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PMID	17979836 ( )
Title	From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey.
Abstract	Death receptors (DRs) are more than simple killers: they control cell growth, proliferation, and survival, thereby playing a pivotal role in immune and inflammatory responses. Some of these phenomena might be explained by aberrant reactive oxygen species (ROS) production and metabolism, which can lead to oxidative stress. A key signaling molecule of DR-initiated intracellular pathways, receptor-interacting protein 1 (RIP1), orchestrates a complex control of multiple responses and may link DR-associated signaling complexes to ROS production by mitochondria. Yet, RIP1 is also an important regulator of endogenous anti-oxidants and ROS scavenging enzymes, because it is required for nuclear factor kappaB activation that results in expression of anti-apoptotic and anti-oxidant proteins. Alteration of RIP1 function may result in ROS accumulation and abnormal c-Jun N-terminal protein kinase activation, affecting inflammatory responses, innate immunity, stress responses, and cell survival. These molecular mechanisms may be involved in neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.

NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.

Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	55	rip1 \| RIP1-dependent \| RIP1-mediated \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	47	NF-kappaB-dependent \| NF-kappaB-activated \|
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	43	TNFA-mediated \| TNF-related \| tumor necrosis factor \| TNFA-induced \| TNF-induced \|
6881	MAPK8	mitogen-activated protein kinase 8	34	JNK \| JNK1 \| JNK-dependent \| JNK-induced \| Jnk1 \|
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	29	c-FLIP \| c flip \|
11180	SOD2	superoxide dismutase 2, mitochondrial	11	manganese superoxide dismutase \| MnSOD \| SOD2 \|
6871	MAPK1	mitogen-activated protein kinase 1	10	ERK \| MAPKs \| p38 \| MAPK \|
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	9	caspase 8 \|
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	9	Nox2 \| NOX2 \| gp91 phox \|
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	8	ANT-conducted \| ANT-cyclophilin \|
990	BCL2	B-cell CLL/lymphoma 2	8	Bcl-2 \| bcl2 \| bcl 2 \| Bcl2 \|
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	8	Ncf1 \| neutrophil cytosolic factor 1 \| p47 \| p47phox \|
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	7	TNFR-mediated \| TNFR1 \| TNFRs \|
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	7	p52 \| Shc \| p66 \|
19986	CYCS	cytochrome c, somatic	7	cytochrome c \|
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	6	IKKB \| IKKB- \| IKKB-deficient \|
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	6	apoptosis inducing factor \| AIF \|
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	6	cyclophilin d \|
11920	FAS	Fas (TNF receptor superfamily, member 6)	6	CD95 \| Fas \| Fas-associated \|
11850	TLR4	toll-like receptor 4	6	TLR4-induced \|
2577	CYBA	cytochrome b-245, alpha polypeptide	6	p22 phox \|
6204	JUN	jun oncogene	5	AP-1 \| c jun \| c-Jun \|
2595	CYP1A1	cytochrome P450, family 1, subfamily A, polypeptide 1	5	CYP \| cytochrome p 450 \| CYPs \|
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	5	Nox5 \| nadph oxidase \|
4095	GADD45A	growth arrest and DNA-damage-inducible, alpha	4	gadd45 \|
992	BCL2L1	BCL2-like 1	4	bcl x \| Bcl-X \| bcl xl \|
11904	TNFRSF10A	tumor necrosis factor receptor superfamily, member 10a	4	tnf related apoptosis inducing ligand receptor 1 \| DR4- \| TRAIL-R1 \|
11905	TNFRSF10B	tumor necrosis factor receptor superfamily, member 10b	4	TRAIL-R2 \| DR5 \| trail r2 \| DR5-mediated \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	4	SOD1 \| SOD \|
19404	NOXO1	NADPH oxidase organizer 1	3	NOXO1 \| nadph oxidase organizer 1 \|
3573	FADD	Fas (TNFRSF6)-associated via death domain	3	FADD \|
7427	MT-CYB	mitochondrially encoded cytochrome b	3	cytochrome b \|
11908	TNFRSF11A	tumor necrosis factor receptor superfamily, member 11a, NFKB activator	3	RANK \|
5992	IL1B	interleukin 1, beta	3	il 1b \| IL-1B \|
1516	CAT	catalase	3	catalase \|
6857	MAP3K5	mitogen-activated protein kinase kinase kinase 5	3	ASK1 \|
12030	TRADD	TNFRSF1A-associated via death domain	3	TRADD \|
991	BCL2A1	BCL2-related protein A1	3	Bfl1 \| Bfl-1 \|
7889	NOX1	NADPH oxidase 1	3	Nox1-generated \|
592	XIAP	X-linked inhibitor of apoptosis	3	XIAP \|
9955	RELA	v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian)	3	p65 \| RelA \|
7891	NOX4	NADPH oxidase 4	3	Nox4 \|
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	2	p67 phox \|
1974	CHUK	conserved helix-loop-helix ubiquitous kinase	2	IKKA \|
2434	CSF2	colony stimulating factor 2 (granulocyte-macrophage)	2	gm csf \| GM-CSF \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	2	Rac \| Akt-1 \|
13273	DUOX2	dual oxidase 2	2	DUOX2 \| Duox2 \|
8584	SERPINB2	serpin peptidase inhibitor, clade B (ovalbumin), member 2	2	pai 2 \| PAI-2 \|
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	2	p50 \| CD40 \|
6025	IL8	interleukin 8	2	IL-8 \| il 8 \|
12036	TRAF6	TNF receptor-associated factor 6	2	TRAF6 \|
9719	PEX5	peroxisomal biogenesis factor 5	2	PEX5 \|
9801	RAC1	ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)	2	Rac1 \|
7551	MYBPC3	myosin binding protein C, cardiac	2	FHC \|
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	2	P450 \| P-450 \|
3017	DR1	down-regulator of transcription 1, TBP-binding (negative cofactor 2)	2	DR1 \|
21528	DIABLO	diablo homolog (Drosophila)	2	DIABLO \| Smac \|
7890	NOX3	NADPH oxidase 3	2	Nox3 \|
7562	MYD88	myeloid differentiation primary response gene (88)	2	Myd88 \|
2527	CTSB	cathepsin B	1	cathepsin b \|
9208	POR	P450 (cytochrome) oxidoreductase	1	cytochrome p450 reductase \|
10680	SDHA	succinate dehydrogenase complex, subunit A, flavoprotein (Fp)	1	succinate dehydrogenase complex \|
1503	CASP2	caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2)	1	caspase 2 \|
3768	FMN1	formin 1	1	FMN-containing \|
3062	DUOX1	dual oxidase 1	1	Duox1 \|
12518	UCP2	uncoupling protein 2 (mitochondrial, proton carrier)	1	UCP2 \|
11896	TNFAIP3	tumor necrosis factor, alpha-induced protein 3	1	A20 \|
21148	RNF123	ring finger protein 123	1	ubiquitin ligase \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	1	ap 1 \|
12435	TXN	thioredoxin	1	thioredoxin \|
8975	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	1	PI3K \|
6943	MCL1	myeloid cell leukemia sequence 1 (BCL2-related)	1	Mcl-1 \|
2570	CYB5A	cytochrome b5 type A (microsomal)	1	cytochrome b 5 \|
8988	PIN1	peptidylprolyl cis/trans isomerase, NIMA-interacting 1	1	prolyl isomerase \|
2727	DDO	D-aspartate oxidase	1	d aspartate oxidase \|
12805	XDH	xanthine dehydrogenase	1	xanthine oxidase \|
8017	NSMAF	neutral sphingomyelinase (N-SMase) activation associated factor	1	FAN \|
6081	INS	insulin	1	insulin \|
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	1	STAT1 \|
11910	TNFRSF25	tumor necrosis factor receptor superfamily, member 25	1	DR3 \|
9956	RELB	v-rel reticuloendotheliosis viral oncogene homolog B, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (avian)	1	RelB \|
2726	DDIT3	DNA-damage-inducible transcript 3	1	growth arrest and dna damage inducible \|
1500	CASP10	caspase 10, apoptosis-related cysteine peptidase	1	fas associated death domain protein \|
11121	SMPD2	sphingomyelin phosphodiesterase 2, neutral membrane (neutral sphingomyelinase)	1	nSMase \|
8124	OGDH	oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide)	1	A-KGDH \|
5993	IL1R1	interleukin 1 receptor, type I	1	IL-1R1 \|
5438	IFNG	interferon, gamma	1	IFNG-induced \|
3423	EPX	eosinophil peroxidase	1	eosinophil peroxidase \|
11562	TANK	TRAF family member-associated NFKB activator	1	TRAF2 \|
5014	HMOX2	heme oxygenase (decycling) 2	1	ho 2 \|
2631	CYP2E1	cytochrome P450, family 2, subfamily E, polypeptide 1	1	CYP2E1 \|
7218	MPO	myeloperoxidase	1	myeloperoxidase \|
11181	SOD3	superoxide dismutase 3, extracellular	1	SOD3 \|
2671	DAO	D-amino-acid oxidase	1	d amino acid oxidase \|
31395	COX8B	cytochrome c oxidase, subunit 8B pseudogene	1	cytochrome c oxidase \|
949	BAK1	BCL2-antagonist/killer 1	1	Bak \|
11929	TNFSF13B	tumor necrosis factor (ligand) superfamily, member 13b	1	b cell activating factor \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	signaling molecule of DR-initiated intracellular pathways receptor-interacting protein 1 (RIP1), RIP1 orchestrates a complex control of multiple responses and may link
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Yet RIP1 is also an important regulator of endogenous anti-oxidants and ROS
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Alteration of RIP1 function may result in ROS accumulation and abnormal c-Jun N-terminal
6204	JUN	jun oncogene	c-Jun	2.8	of RIP1 function may result in ROS accumulation and abnormal c-Jun N-terminal protein kinase activation affecting inflammatory responses innate immunity stress
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFRs	2.7	of a large family of tumor necrosis factor receptors (TNFRs) TNFRs ( 1
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR	2.7	The TNFR family consists of more than 20 members including CD40 receptor
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	CD40	1.4	The TNFR family consists of more than 20 members including CD40 receptor activator of nuclear factor kappaB (RANK), RANK B-cell activating
11908	TNFRSF11A	tumor necrosis factor receptor superfamily, member 11a, NFKB activator	RANK	2.2	members including CD40 receptor activator of nuclear factor kappaB (RANK), RANK B-cell activating factor belonging to the TNF family receptor ectodysplasin
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	2.7	factor kappaB (RANK), RANK B-cell activating factor belonging to the TNF family receptor ectodysplasin receptor type I TNF receptor (TNFRI) TNFRI
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	2.7	belonging to the TNF family receptor ectodysplasin receptor type I TNF receptor (TNFRI) TNFRI (DR1), DR1 TNFRII Fas (CD95 CD95 or
3017	DR1	down-regulator of transcription 1, TBP-binding (negative cofactor 2)	DR1	0.3	receptor ectodysplasin receptor type I TNF receptor (TNFRI) TNFRI (DR1), DR1 TNFRII Fas (CD95 CD95 or DR2 DR3 DR4 TNF-related apoptosis-inducing
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	receptor type I TNF receptor (TNFRI) TNFRI (DR1), DR1 TNFRII Fas (CD95 CD95 or DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor
11920	FAS	Fas (TNF receptor superfamily, member 6)	CD95	2.1	I TNF receptor (TNFRI) TNFRI (DR1), DR1 TNFRII Fas (CD95 CD95 or DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)],
11910	TNFRSF25	tumor necrosis factor receptor superfamily, member 25	DR3	1.2	(TNFRI) TNFRI (DR1), DR1 TNFRII Fas (CD95 CD95 or DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)], TRAIL-R1 DR5 (TRAIL-R2),
11904	TNFRSF10A	tumor necrosis factor receptor superfamily, member 10a	DR4	1.2	TNFRI (DR1), DR1 TNFRII Fas (CD95 CD95 or DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)], TRAIL-R1 DR5 (TRAIL-R2), TRAIL-R2
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-related	2.7	(DR1), DR1 TNFRII Fas (CD95 CD95 or DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)], TRAIL-R1 DR5 (TRAIL-R2), TRAIL-R2 which
11904	TNFRSF10A	tumor necrosis factor receptor superfamily, member 10a	TRAIL-R1	1.2	or DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)], TRAIL-R1 DR5 (TRAIL-R2), TRAIL-R2 which control cell proliferation survival death growth
11905	TNFRSF10B	tumor necrosis factor receptor superfamily, member 10b	DR5	2.7	DR2 DR3 DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)], TRAIL-R1 DR5 (TRAIL-R2), TRAIL-R2 which control cell proliferation survival death growth and
11905	TNFRSF10B	tumor necrosis factor receptor superfamily, member 10b	TRAIL-R2	2.7	DR4 TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1)], TRAIL-R1 DR5 (TRAIL-R2), TRAIL-R2 which control cell proliferation survival death growth and immune response
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR	2.7	receptors that mediate cell death also exist outside of the TNFR family
3017	DR1	down-regulator of transcription 1, TBP-binding (negative cofactor 2)	DR1	0.3	studies of one particular DR the TNFRI also known as DR1 and a protein kinase originally identified as a critical component
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	component of TNFRI and DR signaling receptor-interacting protein 1 (RIP1) RIP1 ( 27
8124	OGDH	oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide)	A-KGDH	0.3	be generated by mitochondrial dehydrogenases such as A-ketoglutarate dehydrogenase (A-KGDH) A-KGDH ( 33 and succinate dehydrogenase (complex complex II ( 34
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	AIF	0.6	Furthermore apoptosis-inducing factor (AIF), AIF which is critical for complex I activity ( 36 upon
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	AIF	0.6	The loss of mitochondrial AIF therefore may be a cause of increased mitochondrial ROS production
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	AIF	0.6	AIF was reported to possess NADH oxidase activity enabling O 2
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	AIF	0.6	Once released in the cytosol AIF may also generate O 2 _amp_#8226 _amp_#8722 ( 38
12518	UCP2	uncoupling protein 2 (mitochondrial, proton carrier)	UCP2	0.6	Moreover activation of mitochondrial uncoupling proteins such as UCP2 may decrease ROS production ( 42
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	p66	0.3	it was reported that a mitochondrial intermembrane space-localized redox enzyme p66 Shc oxidizes cytochrome c and generates H 2 O 2
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	Shc	0.3	was reported that a mitochondrial intermembrane space-localized redox enzyme p66 Shc oxidizes cytochrome c and generates H 2 O 2 in
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	2.4	H 2 O 2 by matrix manganese superoxide dismutase (MnSOD), MnSOD also termed SOD2 ( 45 whereas O 2 _amp_#8226 _amp_#8722
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	2 by matrix manganese superoxide dismutase (MnSOD), MnSOD also termed SOD2 ( 45 whereas O 2 _amp_#8226 _amp_#8722 released to the
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	1.4	the intramembrane space is partly dismutated by intermembrane Cu Zn SOD also termed SOD1 ( 46 ( Fig 1
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.4	is partly dismutated by intermembrane Cu Zn SOD also termed SOD1 ( 46 ( Fig 1
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.4	53 cytosolic scavenger enzymes such as catalase peroxiredoxin (I), I SOD1 and GPX ( 53 54
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	1.4	Detoxification of ROS by extracellular Cu Zn SOD (SOD3) SOD3 is an additional mechanism of ROS elimination (
11181	SOD3	superoxide dismutase 3, extracellular	SOD3	0.9	Detoxification of ROS by extracellular Cu Zn SOD (SOD3) SOD3 is an additional mechanism of ROS elimination ( 54
9719	PEX5	peroxisomal biogenesis factor 5	PEX5	0.8	mouse model of Zellweger syndrome was developed by disrupting the PEX5 gene encoding the targeting receptor for most peroxisomal matrix proteins
9719	PEX5	peroxisomal biogenesis factor 5	PEX5	0.8	PEX5 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice have a severe peroxisomal import defect
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	P-450	1.9	Non-specific monooxygenases the cytochrome P-450 enzymes (CYPs), CYPs are membrane-bound terminal oxidases present mainly in
2595	CYP1A1	cytochrome P450, family 1, subfamily A, polypeptide 1	CYPs	1.2	Non-specific monooxygenases the cytochrome P-450 enzymes (CYPs), CYPs are membrane-bound terminal oxidases present mainly in the ER as
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	P450	1.9	a multi-enzyme system which also includes FAD/FMN-containing FAD FMN-containing NADPH-cytochrome P450 reductase and cytochrome b 5
3768	FMN1	formin 1	FMN-containing	0.4	components of a multi-enzyme system which also includes FAD/FMN-containing FAD FMN-containing NADPH-cytochrome P450 reductase and cytochrome b 5
2595	CYP1A1	cytochrome P450, family 1, subfamily A, polypeptide 1	CYP	1.2	Members of the CYP superfamily encompassing more than 30 genes ( 61 catalyze substrate
2595	CYP1A1	cytochrome P450, family 1, subfamily A, polypeptide 1	CYPs	1.2	The vast majority of CYPs are expressed in the liver including the ethanol-induced CYP2E1 (
2631	CYP2E1	cytochrome P450, family 2, subfamily E, polypeptide 1	CYP2E1	1.2	of CYPs are expressed in the liver including the ethanol-induced CYP2E1 ( 63 where they participate in drug metabolism but CYPs
2595	CYP1A1	cytochrome P450, family 1, subfamily A, polypeptide 1	CYPs	1.2	CYP2E1 ( 63 where they participate in drug metabolism but CYPs expressed in extrahepatic tissues especially in the gastrointestinal tract may
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.3	b 558 a catalytic gp91 phox subunit (also also termed Nox2 and a p22 phox subunit as well as cytosolic components
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.3	catalytic gp91 phox subunit (also also termed Nox2 and a p22 phox subunit as well as cytosolic components p47 phox and
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.9	and a p22 phox subunit as well as cytosolic components p47 phox and p67 phox and the small GTPase Rac1 (
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	phox subunit as well as cytosolic components p47 phox and p67 phox and the small GTPase Rac1 ( 65
9801	RAC1	ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)	Rac1	0.0	components p47 phox and p67 phox and the small GTPase Rac1 ( 65
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.3	Nox2 and other members of the Nox family Nox1 Nox3 Nox4
7889	NOX1	NADPH oxidase 1	Nox1	0.9	Nox2 and other members of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox2 and other members of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic cells
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox2 and other members of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic cells (
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	and other members of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic cells ( 65
3062	DUOX1	dual oxidase 1	Duox1	0.3	other members of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic cells ( 65 66
13273	DUOX2	dual oxidase 2	DUOX2	0.3	other members of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic cells ( 65 66
13273	DUOX2	dual oxidase 2	Duox2	0.3	of the Nox family Nox1 Nox3 Nox4 Nox5 Duox1 and Duox2 were found in non-phagocytic cells ( 65 66
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.3	lipid rafts cluster at the membrane which is important for Nox2 activation ( 67
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.9	This event is followed by translocation of gp91 phox and p47 phox aggregation and activation of NADPH oxidases
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.3	A crucial event in activation of Nox2 is phosphorylation of p47 phox which allows its interaction with
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.9	A crucial event in activation of Nox2 is phosphorylation of p47 phox which allows its interaction with p22 phox and binding
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.3	is phosphorylation of p47 phox which allows its interaction with p22 phox and binding to cytochrome b 558 ( 65
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	It was proposed that TNFA-induced PI3K activation with consequent PKC_amp_#x03B6 activation are required for p47
8975	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	PI3K	1.3	It was proposed that TNFA-induced PI3K activation with consequent PKC_amp_#x03B6 activation are required for p47 phox
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.9	TNFA-induced PI3K activation with consequent PKC_amp_#x03B6 activation are required for p47 phox phosphorylation ( 68
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	However it remains unclear whether TNFA-induced Nox activation is essential for cell death
7889	NOX1	NADPH oxidase 1	Nox1	0.9	In contrast to Nox1 and Nox2 which seem to have structural and functional similarities
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX2	2.3	In contrast to Nox1 and Nox2 which seem to have structural and functional similarities
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.3	In contrast to Nox1 and Nox2 which seem to have structural and functional similarities Nox3 is
7890	NOX3	NADPH oxidase 3	Nox3	0.9	and Nox2 which seem to have structural and functional similarities Nox3 is likely to be constitutively active ( 70 even though
19404	NOXO1	NADPH oxidase organizer 1	NOXO1	2.5	by cytosolic proteins such as NADPH oxidase organizer 1 (NOXO1), NOXO1 an isoform of p47 phox ( 70 and Rac1 (
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.9	as NADPH oxidase organizer 1 (NOXO1), NOXO1 an isoform of p47 phox ( 70 and Rac1 ( 71
9801	RAC1	ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)	Rac1	0.0	(NOXO1), NOXO1 an isoform of p47 phox ( 70 and Rac1 ( 71
7891	NOX4	NADPH oxidase 4	Nox4	0.9	The activation mechanism of Nox4 which was found in the nucleus ( 57 is not
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.3	It forms a complex with p22 phox that is not modulated by known cytosolic Nox regulators
19404	NOXO1	NADPH oxidase organizer 1	NOXO1	2.5	is not modulated by known cytosolic Nox regulators such as NOXO1 and Rac ( 72
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Rac	0.1	modulated by known cytosolic Nox regulators such as NOXO1 and Rac ( 72
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	Nox5 activation is fully dependent on Ca which promotes interaction between
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	Ca which promotes interaction between N-terminal and C-terminal domains of Nox5 ( 73
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	Furthermore Ca -activated signaling pathways result in phosphorylation of Nox5 on Thr 494 and Ser 498
21528	DIABLO	diablo homolog (Drosophila)	Smac	1.8	and release of apoptogenic proteins such as cytochrome c Smac/DIABLO, Smac DIABLO and AIF ( 77 as a result of increased
21528	DIABLO	diablo homolog (Drosophila)	DIABLO	1.8	release of apoptogenic proteins such as cytochrome c Smac/DIABLO, Smac DIABLO and AIF ( 77 as a result of increased MOMP
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	AIF	0.6	apoptogenic proteins such as cytochrome c Smac/DIABLO, Smac DIABLO and AIF ( 77 as a result of increased MOMP which is
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	of MOMP may involve components VDAC adenine nucleotide translocase (ANT), ANT etc. of the permeability transition pore (MPTP) MPTP ( 76
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR1	2.7	release in response to oxidative stress increased intracellular Ca and TNFR1 signaling ( 81
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.8	Instead MOMP is suggested to be mediated by pro-apoptotic Bcl-2 family members (e.g e.g Bax Bak Bad Bid acting directly
949	BAK1	BCL2-antagonist/killer 1	Bak	0.0	be mediated by pro-apoptotic Bcl-2 family members (e.g e.g Bax Bak Bad Bid acting directly on the outer mitochondrial membrane (
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	35 44 84 via modification of the thiol groups of ANT and VDAC
12030	TRADD	TNFRSF1A-associated via death domain	TRADD	0.6	I consisting of the adapter TNFRI-associated death domain protein (TRADD), TRADD the protein kinase RIP1 and TNF receptor-associated factor (TRAF) TRAF
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	adapter TNFRI-associated death domain protein (TRADD), TRADD the protein kinase RIP1 and TNF receptor-associated factor (TRAF) TRAF 2 and 5
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	2.7	death domain protein (TRADD), TRADD the protein kinase RIP1 and TNF receptor-associated factor (TRAF) TRAF 2 and 5
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	This complex rapidly signals to activate NF-kappaB through inhibitor of NF-kappaB (IkappaB) IkappaB kinase (IKK) IKK and
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	This complex rapidly signals to activate NF-kappaB through inhibitor of NF-kappaB (IkappaB) IkappaB kinase (IKK) IKK and mitogen-activated protein kinase (MAPK)
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	(IkappaB) IkappaB kinase (IKK) IKK and mitogen-activated protein kinase (MAPK) MAPK cascades which regulate other transcription factors such as AP-1 (
6204	JUN	jun oncogene	AP-1	2.8	(MAPK) MAPK cascades which regulate other transcription factors such as AP-1 ( 87
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB activation inhibits the ability of TNFRI to induce apoptosis by
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	of TNFRI to induce apoptosis by augmenting the synthesis of c-FLIP ( 88 a specific inhibitor of caspase 8/10 8 10
12030	TRADD	TNFRSF1A-associated via death domain	TRADD	0.6	dissociates from the receptor and a cytoplasmic complex of the TRADD and TRAF2 and RIP1 is then available to associate with
11562	TANK	TRAF family member-associated NFKB activator	TRAF2	1.6	the receptor and a cytoplasmic complex of the TRADD and TRAF2 and RIP1 is then available to associate with the Fas-associated
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	and a cytoplasmic complex of the TRADD and TRAF2 and RIP1 is then available to associate with the Fas-associated death domain
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas-associated	2.1	TRAF2 and RIP1 is then available to associate with the Fas-associated death domain protein (FADD) FADD to form complex II (
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	0.9	available to associate with the Fas-associated death domain protein (FADD) FADD to form complex II ( 86 which can activate caspase
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	8 10 only in cells that contain low levels of c-FLIP ( 88
8017	NSMAF	neutral sphingomyelinase (N-SMase) activation associated factor	FAN	0.9	Additionally it was suggested that TNFRI-recruited factor-associated neutral sphingomyelinase (FAN) FAN activates a neutral sphingomyelinase (nSMase), nSMase leading to generation of
11121	SMPD2	sphingomyelin phosphodiesterase 2, neutral membrane (neutral sphingomyelinase)	nSMase	1.0	factor-associated neutral sphingomyelinase (FAN) FAN activates a neutral sphingomyelinase (nSMase), nSMase leading to generation of sphingosine ( 90 which may permeabilize
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1-mediated	2.1	RIP1-mediated cell death the bell tolls for mitochondria
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	for caspase 8 activation ( 27 96 ( Fig 2 RIP1 is needed for IKK and NF-kappaB activation ( 97 98
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	96 ( Fig 2 RIP1 is needed for IKK and NF-kappaB activation ( 97 98
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Although RIP1 is a serine/threonine serine threonine kinase ( 99 100 its
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	( 99 100 its protein kinase activity is dispensable for NF-kappaB activation ( 98
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Caspase 8 can cleave RIP1 targeting the aspartic acid at position 324 thereby directing RIP1
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	RIP1 targeting the aspartic acid at position 324 thereby directing RIP1 to induce apoptosis ( 101
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	As a result RIP1 cleavage prevents TNFA-induced NF-kappaB activation and promotes TNFA-induced apoptosis through
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	As a result RIP1 cleavage prevents TNFA-induced NF-kappaB activation and promotes TNFA-induced apoptosis through a RIPc (one
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	As a result RIP1 cleavage prevents TNFA-induced NF-kappaB activation and promotes TNFA-induced apoptosis through a RIPc (one one
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	a result RIP1 cleavage prevents TNFA-induced NF-kappaB activation and promotes TNFA-induced apoptosis through a RIPc (one one of the cleavage products
12030	TRADD	TNFRSF1A-associated via death domain	TRADD	0.6	RIPc (one one of the cleavage products -enhanced interaction between TRADD FADD and caspase 8 ( 101 ( Fig 2
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	0.9	(one one of the cleavage products -enhanced interaction between TRADD FADD and caspase 8 ( 101 ( Fig 2
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	RIP1 cleavage was also detected after activation of other DRs (
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	RIP1 kinase activity however may be required for DR-induced non-apoptotic cell
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	However this has not been fully validated and RIP1 substrates involved in cell death are yet to be identified
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Overexpression of either wildtype RIP1 or a RIP1 mutant lacking the kinase domain induced cell
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Overexpression of either wildtype RIP1 or a RIP1 mutant lacking the kinase domain induced cell death ( 103
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	the kinase domain induced cell death ( 103 however the RIP1 kinase domain seems to be involved in c-Jun N-terminal protein
6204	JUN	jun oncogene	c-Jun	2.8	however the RIP1 kinase domain seems to be involved in c-Jun N-terminal protein kinase (JNK) JNK activation ( 27 which may
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	seems to be involved in c-Jun N-terminal protein kinase (JNK) JNK activation ( 27 which may facilitate MOMP upon TNFRI-mediated apoptosis
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	which may facilitate MOMP upon TNFRI-mediated apoptosis through promotion of c-FLIP degradation ( 88
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	TNFA is still able to activate JNK in RIP1-deficient cells (
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	TNFA is still able to activate JNK in RIP1-deficient cells ( 104 even though this activation is
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Furthermore RIP1 may be involved in activation of caspase 2 ( 105
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt-1	0.0	be involved in activation of caspase 2 ( 105 and Akt-1 ( 106 and their activity might be crucial in modulation
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	In monocytic cells TNFA-induced RIP1-dependent inhibition of ANT-conducted ADP transport into mitochondria led to
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1-dependent	2.1	In monocytic cells TNFA-induced RIP1-dependent inhibition of ANT-conducted ADP transport into mitochondria led to progressively
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT-conducted	0.6	In monocytic cells TNFA-induced RIP1-dependent inhibition of ANT-conducted ADP transport into mitochondria led to progressively reduced ATP levels
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	TNFA induced dissociation of mitochondrial matrix peptidyl-prolyl isomerase ( 109 cyclophilin
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	of mitochondrial matrix peptidyl-prolyl isomerase ( 109 cyclophilin D from ANT
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	to be crucial for binding of zVAD.fmk to cys56 of ANT thereby preventing ANT from adopting a _amp_#8216 cytosolic_amp_#8217 conformation that
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	for binding of zVAD.fmk to cys56 of ANT thereby preventing ANT from adopting a _amp_#8216 cytosolic_amp_#8217 conformation that enables ADP/ATP ADP
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1-mediated	2.1	However because anti-oxidants failed to alter RIP1-mediated cell death ( 85 a role for other ROS cannot
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Because RIP1 trafficked to mitochondria after TNFA stimulation of cells cytochrome c
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	Because RIP1 trafficked to mitochondria after TNFA stimulation of cells cytochrome c release was not observed and
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	It was therefore proposed that RIP1 may initiate a new mitochondrial pathway that is not dependent
3573	FADD	Fas (TNFRSF6)-associated via death domain	FADD	0.9	mitochondrial pathway that is not dependent on complex II and FADD caspase 8 interaction ( 85
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Our recent unpublished data suggest that traffic and association of RIP1 with mitochondria may be modulated by NF-kappaB signaling ( Fig
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	and association of RIP1 with mitochondria may be modulated by NF-kappaB signaling ( Fig 3
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Nonetheless the mechanisms by which RIP1 affects the ANT-cyclophilin D complex as well as the mitochondrial
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT-cyclophilin	0.6	Nonetheless the mechanisms by which RIP1 affects the ANT-cyclophilin D complex as well as the mitochondrial target of RIP1
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	ANT-cyclophilin D complex as well as the mitochondrial target of RIP1 are yet to be identified
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	Cyclophilin D-null cells are as sensitive as wildtype cells to TNFA or pro-apoptotic Bcl-2 family member-induced cell death ( 111 but
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.8	are as sensitive as wildtype cells to TNFA or pro-apoptotic Bcl-2 family member-induced cell death ( 111 but exhibit increased sensitivity
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	certain myopathies ( 114 altered expression or function of either ANT or cyclophilin D is observed
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	in TNFRI-mediated apoptotic and non-apoptotic cell death through prolongation of JNK activity ( 15 increase of MOMP and lysosome membrane permeabilization
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	ROS are also essential for Fas DR4- and DR5-mediated non-apoptotic cell death ( 14 102
11904	TNFRSF10A	tumor necrosis factor receptor superfamily, member 10a	DR4-	1.2	ROS are also essential for Fas DR4- and DR5-mediated non-apoptotic cell death ( 14 102
11905	TNFRSF10B	tumor necrosis factor receptor superfamily, member 10b	DR5-mediated	2.7	ROS are also essential for Fas DR4- and DR5-mediated non-apoptotic cell death ( 14 102
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	However sustained ROS accumulation depends on either compromised NF-kappaB activation ( 15 16 caspase inhibition ( 102 or suppression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-mediated	2.7	Unlike TNFA-mediated NF-kappaB activation ( 115 IL-1B-mediated activation of NF-kappaB was suggested
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Unlike TNFA-mediated NF-kappaB activation ( 115 IL-1B-mediated activation of NF-kappaB was suggested to
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Unlike TNFA-mediated NF-kappaB activation ( 115 IL-1B-mediated activation of NF-kappaB was suggested to require ROS production by Nox2 ( 116
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.3	activation of NF-kappaB was suggested to require ROS production by Nox2 ( 116
12036	TRAF6	TNF receptor-associated factor 6	TRAF6	1.2	ROS were proposed to be essential for TRAF6 recruitment by the IL-1R1/Myd88 IL-1R1 Myd88 signaling complex ( 116
7562	MYD88	myeloid differentiation primary response gene (88)	Myd88	0.6	to be essential for TRAF6 recruitment by the IL-1R1/Myd88 IL-1R1 Myd88 signaling complex ( 116
5993	IL1R1	interleukin 1 receptor, type I	IL-1R1	0.3	proposed to be essential for TRAF6 recruitment by the IL-1R1/Myd88 IL-1R1 Myd88 signaling complex ( 116
12036	TRAF6	TNF receptor-associated factor 6	TRAF6	1.2	Notably recruitment of TRAF6 to TLR4 a receptor related to IL-1R which ultimately activates
11850	TLR4	toll-like receptor 4	TLR4	1.3	Notably recruitment of TRAF6 to TLR4 a receptor related to IL-1R which ultimately activates ASK1 and
6857	MAP3K5	mitogen-activated protein kinase kinase kinase 5	ASK1	2.2	to TLR4 a receptor related to IL-1R which ultimately activates ASK1 and p38 MAPK is also dependent on ROS ( 117
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	a receptor related to IL-1R which ultimately activates ASK1 and p38 MAPK is also dependent on ROS ( 117
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	receptor related to IL-1R which ultimately activates ASK1 and p38 MAPK is also dependent on ROS ( 117
11850	TLR4	toll-like receptor 4	TLR4	1.3	TLR4 may use Myd88 for activation of Nox ( 118 and
7562	MYD88	myeloid differentiation primary response gene (88)	Myd88	0.6	TLR4 may use Myd88 for activation of Nox ( 118 and ROS production was
11850	TLR4	toll-like receptor 4	TLR4-induced	1.3	118 and ROS production was proposed to be involved in TLR4-induced NF-kappaB activation ( 119 120 and IL-8 production ( 120
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	and ROS production was proposed to be involved in TLR4-induced NF-kappaB activation ( 119 120 and IL-8 production ( 120
6025	IL8	interleukin 8	IL-8	1.0	be involved in TLR4-induced NF-kappaB activation ( 119 120 and IL-8 production ( 120
11850	TLR4	toll-like receptor 4	TLR4	1.3	Another mechanism that might explain Nox involvement in TLR4 signaling was recently described ( 121
7891	NOX4	NADPH oxidase 4	Nox4	0.9	It presumes direct interaction between the C-terminal region of Nox4 and the cytoplasmic tail of TLR4 ( 121
11850	TLR4	toll-like receptor 4	TLR4	1.3	the C-terminal region of Nox4 and the cytoplasmic tail of TLR4 ( 121
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR	2.7	A member of the TNFR family RANK is a critical regulator of osteoclast differentiation
11908	TNFRSF11A	tumor necrosis factor receptor superfamily, member 11a, NFKB activator	RANK	2.2	A member of the TNFR family RANK is a critical regulator of osteoclast differentiation
11908	TNFRSF11A	tumor necrosis factor receptor superfamily, member 11a, NFKB activator	RANK	2.2	RANK engagement was suggested to increase Nox1-generated ROS and thereby promote
7889	NOX1	NADPH oxidase 1	Nox1-generated	0.9	RANK engagement was suggested to increase Nox1-generated ROS and thereby promote MAPK activation and osteoclastogenesis ( 122
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	engagement was suggested to increase Nox1-generated ROS and thereby promote MAPK activation and osteoclastogenesis ( 122 ( Table 1
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	p66	0.3	Another potential candidate source of ROS in DR signaling is p66 Shc a putative mitochondrial redox enzyme which generates mitochondrial ROS
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	Shc	0.3	potential candidate source of ROS in DR signaling is p66 Shc a putative mitochondrial redox enzyme which generates mitochondrial ROS in
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	p66	0.3	However it is presently unknown whether p66 Shc is involved in DR signaling
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	Shc	0.3	However it is presently unknown whether p66 Shc is involved in DR signaling
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Increased ROS levels and sustained JNK activation a harbinger of death
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Prolonged JNK activation is required for TNFA-induced death ( 15 16 88
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	Prolonged JNK activation is required for TNFA-induced death ( 15 16 88 123-126
6881	MAPK8	mitogen-activated protein kinase 8	Jnk1	2.7	We found that Jnk1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice are protected against TNFR-mediated liver failure
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR-mediated	2.7	found that Jnk1 _amp_#8722;/_amp_#8722; _amp_#8722 _amp_#8722 mice are protected against TNFR-mediated liver failure and lethality elicited by administration of concanavalin A
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	by administration of concanavalin A which induces expression of cell-bound TNFA by NK and T cells and leads to activation of
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	The question however is how JNK activation promotes cell death
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	It was proposed that JNK activation somehow promotes processing of the BH3-domain protein Bid to
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	which akin to caspase 8-cleaved Bid tBid ( 129 allows TNFA-induced apoptosis to proceed ( Fig 2
6881	MAPK8	mitogen-activated protein kinase 8	JNK-dependent	2.7	Nonetheless a JNK-dependent phosphorylation event that directly controls Bid processing has not been
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	Moreover TNFA-induced MOMP and cell death toxicity may be Bid independent (
6881	MAPK8	mitogen-activated protein kinase 8	JNK1	2.7	By examining the effect of JNK1 on proteins known to be involved in TNFRI signaling we
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	known to be involved in TNFRI signaling we found that JNK activity controls TNFA-induced death through the induced proteasomal degradation of
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	involved in TNFRI signaling we found that JNK activity controls TNFA-induced death through the induced proteasomal degradation of c-FLIP ( 88
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	activity controls TNFA-induced death through the induced proteasomal degradation of c-FLIP ( 88
6881	MAPK8	mitogen-activated protein kinase 8	JNK1	2.7	JNK1 however does not phosphorylate c-FLIP itself and instead leads to
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	JNK1 however does not phosphorylate c-FLIP itself and instead leads to phosphorylation-dependent activation of the ubiquitin
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	Itch specifically interacts with the long isoform of c-FLIP c-FLIP L to promote its polyubiquitination and proteasomal degradation
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	Itch specifically interacts with the long isoform of c-FLIP c-FLIP L to promote its polyubiquitination and proteasomal degradation
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Thus whereas NF-kappaB activation prevents TNFA-induced cell death by increasing the intracellular concentration
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	Thus whereas NF-kappaB activation prevents TNFA-induced cell death by increasing the intracellular concentration of c-FLIP L
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	prevents TNFA-induced cell death by increasing the intracellular concentration of c-FLIP L ( 88 89 prolonged JNK activation promotes TNFA-induced death
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	the intracellular concentration of c-FLIP L ( 88 89 prolonged JNK activation promotes TNFA-induced death by decreasing the concentration of c-FLIP
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	of c-FLIP L ( 88 89 prolonged JNK activation promotes TNFA-induced death by decreasing the concentration of c-FLIP L ( 88
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	JNK activation promotes TNFA-induced death by decreasing the concentration of c-FLIP L ( 88 an inhibitor of TNFRI-induced cell death (
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	In addition to elevating c-FLIP L concentrations through transcriptional activation of the c-FLIP gene NF-kappaB
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	to elevating c-FLIP L concentrations through transcriptional activation of the c-FLIP gene NF-kappaB activation maintains high levels of c-FLIP L by
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	c-FLIP L concentrations through transcriptional activation of the c-FLIP gene NF-kappaB activation maintains high levels of c-FLIP L by preventing persistent
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	of the c-FLIP gene NF-kappaB activation maintains high levels of c-FLIP L by preventing persistent JNK activation ( 88
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	activation maintains high levels of c-FLIP L by preventing persistent JNK activation ( 88
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	The exact mechanism by which NF-kappaB controls JNK activation will be described below but in this
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	The exact mechanism by which NF-kappaB controls JNK activation will be described below but in this context it
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	in this context it is important to mention that sustained JNK activation like TNFA-induced cell death depends on TNFA-induced ROS (
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	it is important to mention that sustained JNK activation like TNFA-induced cell death depends on TNFA-induced ROS ( 15
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	that sustained JNK activation like TNFA-induced cell death depends on TNFA-induced ROS ( 15
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Furthermore sustained JNK activation alone does not lead to cell death even in
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKKB	1.9	to cell death even in cells that are deficient in IKKB and therefore cannot mount NF-kappaB activation
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	cells that are deficient in IKKB and therefore cannot mount NF-kappaB activation
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	We have shown that sustained JNK activation needs to cooperate with another yet-to-be identified signal that
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	ROS production promotes prolonged JNK activation ( 132 133
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Although ROS can affect JNK activity through more than one mechanism ( 15 132-135 the
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	mechanism ( 15 132-135 the major mechanism entails inhibition of MAPK phosphatases (MKPs), MKPs the enzymes involved in inactivation of JNK
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	MAPK phosphatases (MKPs), MKPs the enzymes involved in inactivation of JNK and other MAPKs whose activation is also enhanced by TNFRI-induced
6871	MAPK1	mitogen-activated protein kinase 1	MAPKs	2.2	MKPs the enzymes involved in inactivation of JNK and other MAPKs whose activation is also enhanced by TNFRI-induced ROS production (
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Other mechanisms by which ROS can lead to sustained JNK activation may involve activation of the MAPK kinase (MAP3K) MAP3K
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	lead to sustained JNK activation may involve activation of the MAPK kinase (MAP3K) MAP3K ASK1 ( 132
6857	MAP3K5	mitogen-activated protein kinase kinase kinase 5	ASK1	2.2	activation may involve activation of the MAPK kinase (MAP3K) MAP3K ASK1 ( 132
6857	MAP3K5	mitogen-activated protein kinase kinase kinase 5	ASK1	2.2	and others ( 134 failed to find a role for ASK1 in the prolonged TNFA-induced JNK activation that is seen in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	failed to find a role for ASK1 in the prolonged TNFA-induced JNK activation that is seen in NF-kappaB-deficient cells
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	to find a role for ASK1 in the prolonged TNFA-induced JNK activation that is seen in NF-kappaB-deficient cells
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	It has also been argued that prolonged JNK activation may promote ROS generation through an unknown mechanism (
6881	MAPK8	mitogen-activated protein kinase 8	JNK-induced	2.7	it is not clear whether this mechanism is independent of JNK-induced cell death and mitochondrial failure which as discussed above lead
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Role of NF-kappaB in control of cell death and ROS production the guardian
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB in control of cell survival
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB is a collection of dimeric transcription factors that recognize similar
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	In mammals there are five NF-kappaB proteins cRel RelA (p65), p65 RelB NF-kappaB1/p50, NF-kappaB1 p50 and
9955	RELA	v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian)	RelA	0.6	In mammals there are five NF-kappaB proteins cRel RelA (p65), p65 RelB NF-kappaB1/p50, NF-kappaB1 p50 and NF-kappaB2/p52 NF-kappaB2 p52
9955	RELA	v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian)	p65	0.3	In mammals there are five NF-kappaB proteins cRel RelA (p65), p65 RelB NF-kappaB1/p50, NF-kappaB1 p50 and NF-kappaB2/p52 NF-kappaB2 p52
9956	RELB	v-rel reticuloendotheliosis viral oncogene homolog B, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (avian)	RelB	0.3	mammals there are five NF-kappaB proteins cRel RelA (p65), p65 RelB NF-kappaB1/p50, NF-kappaB1 p50 and NF-kappaB2/p52 NF-kappaB2 p52
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	p50	1.4	five NF-kappaB proteins cRel RelA (p65), p65 RelB NF-kappaB1/p50, NF-kappaB1 p50 and NF-kappaB2/p52 NF-kappaB2 p52
10840	SHC1	SHC (Src homology 2 domain containing) transforming protein 1	p52	0.3	RelA (p65), p65 RelB NF-kappaB1/p50, NF-kappaB1 p50 and NF-kappaB2/p52 NF-kappaB2 p52
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB is mainly activated via IKK-dependent phosphorylation and subsequent proteasome-dependent degradation
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	phosphorylation and subsequent proteasome-dependent degradation of IkappaB proteins physically confining NF-kappaB dimers to the cytosol ( 137
1974	CHUK	conserved helix-loop-helix ubiquitous kinase	IKKA	1.0	IKK is composed of three subunits the catalytic subunits IKKA and IKKB and the regulatory subunit IKKG ( 137
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKKB	1.9	is composed of three subunits the catalytic subunits IKKA and IKKB and the regulatory subunit IKKG ( 137
1974	CHUK	conserved helix-loop-helix ubiquitous kinase	IKKA	1.0	Despite extensive structural similarities between IKKA and IKKB most stimuli that lead to NF-kappaB activation including
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKKB	1.9	Despite extensive structural similarities between IKKA and IKKB most stimuli that lead to NF-kappaB activation including TNFRI rely
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	similarities between IKKA and IKKB most stimuli that lead to NF-kappaB activation including TNFRI rely mainly on IKKB activity and IKKB-deficient
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKKB	1.9	that lead to NF-kappaB activation including TNFRI rely mainly on IKKB activity and IKKB-deficient mice and cells exhibit defective TNFA-induced NF-kappaB
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKKB-deficient	1.9	NF-kappaB activation including TNFRI rely mainly on IKKB activity and IKKB-deficient mice and cells exhibit defective TNFA-induced NF-kappaB activation ( 138
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	on IKKB activity and IKKB-deficient mice and cells exhibit defective TNFA-induced NF-kappaB activation ( 138 139
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	IKKB activity and IKKB-deficient mice and cells exhibit defective TNFA-induced NF-kappaB activation ( 138 139
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB was studied originally for its role in activation of innate
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	1996 it became clear that another very critical function of NF-kappaB is inhibition of apoptosis ( 27 139-141
9955	RELA	v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian)	RelA	0.6	The first clue to this important function was provided by RelA knockout mice which die on embryonic day 14.5 due to
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR1	2.7	the liver apoptosis in these mice depends on signaling via TNFR1 and that IKKB- 138 139 and IKKG- 143 deficient mice
5960	IKBKB	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta	IKKB-	1.9	in these mice depends on signaling via TNFR1 and that IKKB- 138 139 and IKKG- 143 deficient mice exhibit similar but
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Currently it is known that NF-kappaB is a transcriptional activator of many anti-apoptotic genes including c-FLIP
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	NF-kappaB is a transcriptional activator of many anti-apoptotic genes including c-FLIP c-IAP-1 c-IAP-2 X chromosome-linked IAP (XIAP), XIAP Bcl-X L A1/Bfl1,
592	XIAP	X-linked inhibitor of apoptosis	XIAP	0.6	anti-apoptotic genes including c-FLIP c-IAP-1 c-IAP-2 X chromosome-linked IAP (XIAP), XIAP Bcl-X L A1/Bfl1, A1 Bfl1 gadd 45B and SOD2 (
992	BCL2L1	BCL2-like 1	Bcl-X	2.0	genes including c-FLIP c-IAP-1 c-IAP-2 X chromosome-linked IAP (XIAP), XIAP Bcl-X L A1/Bfl1, A1 Bfl1 gadd 45B and SOD2 ( 126
991	BCL2A1	BCL2-related protein A1	Bfl1	1.0	c-IAP-2 X chromosome-linked IAP (XIAP), XIAP Bcl-X L A1/Bfl1, A1 Bfl1 gadd 45B and SOD2 ( 126
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	(XIAP), XIAP Bcl-X L A1/Bfl1, A1 Bfl1 gadd 45B and SOD2 ( 126
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB-activated	0.6	As documented above one of the most critical NF-kappaB-activated anti-apoptotic molecules in the contest of TNFRI-induced apoptosis is c-FLIP
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	NF-kappaB-activated anti-apoptotic molecules in the contest of TNFRI-induced apoptosis is c-FLIP ( 131
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	However other NF-kappaB target genes for instance A1/Bfl1 A1 Bfl1 and PAI-2 are
991	BCL2A1	BCL2-related protein A1	Bfl1	1.0	However other NF-kappaB target genes for instance A1/Bfl1 A1 Bfl1 and PAI-2 are more critical for prevention of apoptosis in
8584	SERPINB2	serpin peptidase inhibitor, clade B (ovalbumin), member 2	PAI-2	1.8	other NF-kappaB target genes for instance A1/Bfl1 A1 Bfl1 and PAI-2 are more critical for prevention of apoptosis in response to
11850	TLR4	toll-like receptor 4	TLR4	1.3	critical for prevention of apoptosis in response to activation of TLR4 in macrophages ( 144
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Although the role of NF-kappaB in inhibition of apoptosis is well established it appears that
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	in inhibition of apoptosis is well established it appears that NF-kappaB activation can also prevent necrotic cell death ( 15
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	The mechanisms by which NF-kappaB inhibits necrosis may be related to its effects on mitochondria
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB as a regulator of mitochondrial integrity
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Several NF-kappaB target genes encoding anti-apoptotic proteins may directly modulate mitochondrial function
990	BCL2	B-cell CLL/lymphoma 2	Bcl2	1.3	These proteins are anti-apoptotic members of the Bcl2 family Mcl-1 Bcl-xL and A1/Bfl-1 A1 Bfl-1
6943	MCL1	myeloid cell leukemia sequence 1 (BCL2-related)	Mcl-1	0.3	These proteins are anti-apoptotic members of the Bcl2 family Mcl-1 Bcl-xL and A1/Bfl-1 A1 Bfl-1
991	BCL2A1	BCL2-related protein A1	Bfl-1	1.0	members of the Bcl2 family Mcl-1 Bcl-xL and A1/Bfl-1 A1 Bfl-1
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	Overexpression of Bcl-xL however does not block TNFA-induced cell death MOMP and loss of _amp_#916 _amp_#x03A8 m (
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	and loss of _amp_#916 _amp_#x03A8 m ( 148 suggesting that TNFA also kills cells via a pathway that is not inhibited
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.8	cells via a pathway that is not inhibited by anti-apoptotic Bcl-2 proteins ( 148
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB suppresses formation of the pro-apoptotic complex II ( 86 which
11896	TNFAIP3	tumor necrosis factor, alpha-induced protein 3	A20	1.2	Although several NF-kappaB-regulated genes such as c-IAP1 c-IAP2 A20 and c-FLIP were suggested to mediate the inhibitory effect on
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	Although several NF-kappaB-regulated genes such as c-IAP1 c-IAP2 A20 and c-FLIP were suggested to mediate the inhibitory effect on complex II
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB-dependent	0.6	The NF-kappaB-dependent upregulation of serine protease inhibitor 2A a potent inhibitor of
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	of cathepsin B was shown to provide partial protection from TNFA-induced apoptosis ( 152
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-induced	2.7	However the relationships between this pathway and the main TNFA-induced death pathway which is inhibited by c-FLIP at the level
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c-FLIP	3.3	and the main TNFA-induced death pathway which is inhibited by c-FLIP at the level of caspase 8/10, 8 10 are not
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB as a regulator of anti-oxidant defenses
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB can regulate expression of anti-oxidants such as SOD2 ( 153
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	NF-kappaB can regulate expression of anti-oxidants such as SOD2 ( 153 and ferritin heavy chain (FHC) FHC ( 16
7551	MYBPC3	myosin binding protein C, cardiac	FHC	1.3	such as SOD2 ( 153 and ferritin heavy chain (FHC) FHC ( 16 153 154
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	Unlike other anti-oxidant scavenger enzymes such as GPX and catalase SOD2 is almost exclusively located in the mitochondrial matrix ( 46
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	Mice deficient in SOD2 die within their first week of life demonstrating its importance
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Compromised NF-kappaB activation in vitro and in vivo result in failure to
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	in vitro and in vivo result in failure to induce SOD2 expression thereby increasing ROS accumulation ( 15 16 156
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB-dependent	0.6	We found that NF-kappaB-dependent SOD2 expression prevents oxidation and subsequent inhibition of MKPs by
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	We found that NF-kappaB-dependent SOD2 expression prevents oxidation and subsequent inhibition of MKPs by ROS
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	of MKPs by ROS ( 15 and thereby abrogates prolonged JNK activation ( 15
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	by mitochondrial electron chain ( 157 mimics the effects of SOD2 expression ( 15 suggesting that mitochondria-generated ROS are responsible for
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	( 15 suggesting that mitochondria-generated ROS are responsible for prolonged JNK activation and death of NF-kappaB-deficient cells exposed to TNFA (
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	prolonged JNK activation and death of NF-kappaB-deficient cells exposed to TNFA ( 15
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	also suggested by several groups that the molecular link between NF-kappaB and JNK inhibition is provided by anti-apoptotic NF-kappaB-regulated genes such
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	by several groups that the molecular link between NF-kappaB and JNK inhibition is provided by anti-apoptotic NF-kappaB-regulated genes such as XIAP
592	XIAP	X-linked inhibitor of apoptosis	XIAP	0.6	JNK inhibition is provided by anti-apoptotic NF-kappaB-regulated genes such as XIAP ( 125 and growth arrest and DNA damage-inducible 45B (
4095	GADD45A	growth arrest and DNA-damage-inducible, alpha	gadd45	2.2	( 125 and growth arrest and DNA damage-inducible 45B ( gadd45 B ( 123
592	XIAP	X-linked inhibitor of apoptosis	XIAP	0.6	Nonetheless a molecular target for XIAP in the JNK activation pathway was not found and gadd45
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Nonetheless a molecular target for XIAP in the JNK activation pathway was not found and gadd45 -deficient ( gadd45
4095	GADD45A	growth arrest and DNA-damage-inducible, alpha	gadd45	2.2	XIAP in the JNK activation pathway was not found and gadd45 -deficient ( gadd45 - - mouse embryo fibroblasts are no
4095	GADD45A	growth arrest and DNA-damage-inducible, alpha	gadd45	2.2	JNK activation pathway was not found and gadd45 -deficient ( gadd45 - - mouse embryo fibroblasts are no more susceptible to
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-mediated	2.7	- - mouse embryo fibroblasts are no more susceptible to TNFA-mediated cell death ( 158 than wildtype cells and display normal
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	158 than wildtype cells and display normal (i.e i.e transient JNK activation after TNFA stimulation ( 158 indicating that gadd45 B
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	cells and display normal (i.e i.e transient JNK activation after TNFA stimulation ( 158 indicating that gadd45 B is not essential
4095	GADD45A	growth arrest and DNA-damage-inducible, alpha	gadd45	2.2	transient JNK activation after TNFA stimulation ( 158 indicating that gadd45 B is not essential for the ability of NF-kappaB to
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	that gadd45 B is not essential for the ability of NF-kappaB to prevent sustained JNK activation and apoptosis
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	not essential for the ability of NF-kappaB to prevent sustained JNK activation and apoptosis
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	TNFA and ROS in rheumatoid arthritis
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	TNFA is one of the major mediators of rheumatoid arthritis (RA),
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	Activated NF-kappaB prevents apoptosis of synoviocytes and promotes their hyperproliferation
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-induced	2.7	intracellular ROS ( 166 is thought to be responsible for TNF-induced ROS production by synovial neutrophils in RA ( 167
6871	MAPK1	mitogen-activated protein kinase 1	ERK	2.2	ERK and p38 MAPK whose activity is stimulated by TNFA were
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	ERK and p38 MAPK whose activity is stimulated by TNFA were found to
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	2.2	ERK and p38 MAPK whose activity is stimulated by TNFA were found to phosphorylate
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	ERK and p38 MAPK whose activity is stimulated by TNFA were found to phosphorylate Ser345 of p47phox in response to
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47phox	2.5	is stimulated by TNFA were found to phosphorylate Ser345 of p47phox in response to GM-CSF and TNF respectively
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	2.7	to phosphorylate Ser345 of p47phox in response to GM-CSF and TNF respectively
2434	CSF2	colony stimulating factor 2 (granulocyte-macrophage)	GM-CSF	0.1	were found to phosphorylate Ser345 of p47phox in response to GM-CSF and TNF respectively
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	Ncf1	2.5	decreased ability to produce ROS because of polymorphisms in the Ncf1 locus (which which encodes neutrophil cytosolic factor 1 was reported
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	TNFA ROS and JNK as critical regulators of diabetes
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	TNFA ROS and JNK as critical regulators of diabetes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	immune cells are activated and express proinflammatory cytokines such as TNFA IL-1B and INFG ( 173
5992	IL1B	interleukin 1, beta	IL-1B	0.2	cells are activated and express proinflammatory cytokines such as TNFA IL-1B and INFG ( 173
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	TNFA is a major contributor to pancreatic B-cell loss in T1D
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	to inhibition that further reduces the expression of anti-apoptotic gene NF-kappaB and prevents TNFA IFNG-induced apoptosis of B-cells both in vitro
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA	2.7	further reduces the expression of anti-apoptotic gene NF-kappaB and prevents TNFA IFNG-induced apoptosis of B-cells both in vitro and in vivo
5438	IFNG	interferon, gamma	IFNG-induced	0.3	reduces the expression of anti-apoptotic gene NF-kappaB and prevents TNFA IFNG-induced apoptosis of B-cells both in vitro and in vivo (
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	of IFNG on B-cell apoptosis might be due to excessive Fas and/or and or NO production as a result of STAT1
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	STAT1	0.3	Fas and/or and or NO production as a result of STAT1 activation ( 173 or to transcriptional inhibition that further reduces
11920	FAS	Fas (TNF receptor superfamily, member 6)	Fas	2.1	However both Fas and inducible NO synthase are dispensable for B-cell loss in
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	Sustained JNK activation which may be the consequence of aberrant ROS turnover
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNFA-mediated	2.7	TNFA-mediated insulin-resistance requires increased ROS accumulation ( 179 consistent with its
6881	MAPK8	mitogen-activated protein kinase 8	JNK	2.7	insulin-resistance requires increased ROS accumulation ( 179 consistent with its JNK dependence
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Conclusion puzzles of the day RIP1 association with mitochondria the mechanism by which DR activation may
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	Furthermore the exact role played by RIP1 in mitochondria is far from clear
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	In addition the potential role of NF-kappaB on RIP1 association with mitochondria and how exactly NF-kappaB prevent
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	RIP1	2.7	In addition the potential role of NF-kappaB on RIP1 association with mitochondria and how exactly NF-kappaB prevent formation of
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	of NF-kappaB on RIP1 association with mitochondria and how exactly NF-kappaB prevent formation of complex II need to be elucidated
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	NF-kappaB has been quite well established to facilitate ROS elimination through
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.4	quite well established to facilitate ROS elimination through induction of SOD2 and FHC and possibly other anti-oxidants
7551	MYBPC3	myosin binding protein C, cardiac	FHC	1.3	established to facilitate ROS elimination through induction of SOD2 and FHC and possibly other anti-oxidants
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	2.8	The commonly observed elevation in NF-kappaB activity enhances the expression of anti-apoptotic genes but may also
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	a key signaling molecule of dr initiated intracellular pathways receptor interacting protein 1 rip1 orchestrates a complex control of multiple responses and may link dr associated signaling complexes to ros production by mitochondria.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	yet rip1 is also an important regulator of endogenous anti oxidants and ros scavenging enzymes because it is required for nuclear factor kappab activation that results in expression of anti apoptotic and anti
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	alteration of rip1 function may result in ros accumulation and abnormal c jun n terminal protein kinase activation affecting inflammatory responses innate immunity stress responses and cell survival.
6204	JUN	jun oncogene	c jun	1.0	alteration of rip1 function may result in ros accumulation and abnormal c jun n terminal protein kinase activation affecting inflammatory responses innate immunity stress responses and cell survival.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor	1.0	drs represent a subgroup of a large family of tumor necrosis factor receptors tnfrs 1 .
11904	TNFRSF10A	tumor necrosis factor receptor superfamily, member 10a	tnf related apoptosis inducing ligand receptor 1	1.0	d40 receptor activator of nuclear factor kappab rank b cell activating factor belonging to the tnf family receptor ectodysplasin receptor type i tnf receptor tnfri dr1 tnfrii fas cd95 or dr2 dr3 dr4 [tnf related apoptosis inducing ligand receptor 1 trail r1 ] dr5 trail r2 which control cell proliferation survival death growth and immune response 1 .
11905	TNFRSF10B	tumor necrosis factor receptor superfamily, member 10b	trail r2	1.0	vating factor belonging to the tnf family receptor ectodysplasin receptor type i tnf receptor tnfri dr1 tnfrii fas cd95 or dr2 dr3 dr4 [tnf related apoptosis inducing ligand receptor 1 trail r1 ] dr5 trail r2 which control cell proliferation survival death growth and immune response 1 .
11929	TNFSF13B	tumor necrosis factor (ligand) superfamily, member 13b	b cell activating factor	1.0	the tnfr family consists of more than 20 members including cd40 receptor activator of nuclear factor kappab rank b cell activating factor belonging to the tnf family receptor ectodysplasin receptor type i tnf receptor tnfri dr1 tnfrii fas cd95 or dr2 dr3 dr4 [tnf related apoptosis inducing ligand receptor 1 trail r1 ] dr5 trail r2 whic
5014	HMOX2	heme oxygenase (decycling) 2	ho 2	1.0	ros produced by all types of mammalian cells is a collective term for oxygen radicals primarily superoxide o 2 _amp_#8226; _amp_#8722; and its conjugated acid hydroperoxyl radical ho 2 _amp_#8226; p k a 4.9 as well as hydroxyl oh_amp_#8226; carbonate co 3 _amp_#8226; _amp_#8722; peroxyl ro 2 _amp_#8226; and alkoxyl ro_amp_#8226; radicals and non radical derivates of molecular oxyge
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	conditions 23 ros are continuously generated during normal aerobic metabolism by the mitochondrial electron transport chain fig 1 and during innate immune response by two multi component systems the nadph oxidase and xanthine oxidase complexes 19 24 .
12805	XDH	xanthine dehydrogenase	xanthine oxidase	1.0	are continuously generated during normal aerobic metabolism by the mitochondrial electron transport chain fig 1 and during innate immune response by two multi component systems the nadph oxidase and xanthine oxidase complexes 19 24 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	sm based mainly on studies of one particular dr the tnfri also known as dr1 and a protein kinase originally identified as a critical component of tnfri and dr signaling receptor interacting protein 1 rip1 27 .
10680	SDHA	succinate dehydrogenase complex, subunit A, flavoprotein (Fp)	succinate dehydrogenase complex	1.0	ros may also be generated by mitochondrial dehydrogenases such as a ketoglutarate dehydrogenase a kgdh 33 and succinate dehydrogenase complex ii 34 situated at the inner membrane fig 1 .
8768	AIFM1	apoptosis-inducing factor, mitochondrion-associated, 1	apoptosis inducing factor	1.0	furthermore apoptosis inducing factor aif which is critical for complex i activity 36 upon induction of apoptosis may translocate from mitochondria to the cytosol and to the nucleus 37 38 .
31395	COX8B	cytochrome c oxidase, subunit 8B pseudogene	cytochrome c oxidase	1.0	because cytochrome c delivers electrons from cytochrome bc 1 to cytochrome c oxidase the complete loss of cytochrome c could result in the accumulation of electrons and ros generation 43 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	however a less substantial loss of cytochrome c might generate few ros because cytochrome c may not become limiting 25 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	recently it was reported that a mitochondrial intermembrane space localized redox enzyme p66 shc oxidizes cytochrome c and generates h 2 o 2 in response to different apoptotic stimuli 44 leading to mitochondrial swelling and apoptosis.
11180	SOD2	superoxide dismutase 2, mitochondrial	manganese superoxide dismutase	1.0	o 2 _amp_#8226; _amp_#8722; in the mitochondrial matrix is converted to h 2 o 2 by matrix manganese superoxide dismutase mnsod also termed sod2 45 whereas o 2 _amp_#8226; _amp_#8722; released to the intramembrane space is partly dismutated by intermembrane cu zn sod also termed sod1 46 fig 1 .
12435	TXN	thioredoxin	thioredoxin	1.0	further detoxification of ros is conducted mainly by gluthatione peroxidase gpx 47 as well as thioredoxin reductase tr 48 which use reduced glutathione gsh and thioredoxin txh in the enzymatic reaction fig 1 .
1516	CAT	catalase	catalase	1.0	in heart mitochondria conversion of h 2 o 2 to h 2 o is also regulated by catalase 49 .
1516	CAT	catalase	catalase	1.0	in the cytosol ros are destroyed by peroxisomal detoxification enzymes 53 cytosolic scavenger enzymes such as catalase peroxiredoxin i sod1 and gpx 53 54 .
2727	DDO	D-aspartate oxidase	d aspartate oxidase	1.0	although peroxisomes play an important role in ros elimination peroxisomal oxidases such as acyl coa oxidases d amino acid oxidase d aspartate oxidase and xanthine oxidases transfer hydrogen from their respective substrates to molecular oxygen 24 .
2671	DAO	D-amino-acid oxidase	d amino acid oxidase	1.0	although peroxisomes play an important role in ros elimination peroxisomal oxidases such as acyl coa oxidases d amino acid oxidase d aspartate oxidase and xanthine oxidases transfer hydrogen from their respective substrates to molecular oxygen 24 .
7218	MPO	myeloperoxidase	myeloperoxidase	1.0	these cell types utilize heme peroxidases myeloperoxidase or eosinophil peroxidase that catalyze the formation of the potent and very damaging oxidants hocl and hypobromous acid from h 2 o 2 in the presence of chloride cl _amp_#8722; and bromide br _amp_#87
3423	EPX	eosinophil peroxidase	eosinophil peroxidase	1.0	these cell types utilize heme peroxidases myeloperoxidase or eosinophil peroxidase that catalyze the formation of the potent and very damaging oxidants hocl and hypobromous acid from h 2 o 2 in the presence of chloride cl _amp_#8722; and bromide br _amp_#8722; ions respectively 60
7427	MT-CYB	mitochondrially encoded cytochrome b	cytochrome b	1.0	rome p 450 enzymes cyps are membrane bound terminal oxidases present mainly in the er as components of a multi enzyme system which also includes fad/fmn containing nadph cytochrome p450 reductase and cytochrome b 5 .
2570	CYB5A	cytochrome b5 type A (microsomal)	cytochrome b 5	1.0	rome p 450 enzymes cyps are membrane bound terminal oxidases present mainly in the er as components of a multi enzyme system which also includes fad/fmn containing nadph cytochrome p450 reductase and cytochrome b 5 .
2595	CYP1A1	cytochrome P450, family 1, subfamily A, polypeptide 1	cytochrome p 450	1.0	non specific monooxygenases the cytochrome p 450 enzymes cyps are membrane bound terminal oxidases present mainly in the er as components of a multi enzyme system which also includes fad/fmn containing nadph cytochrome p450 reductase and cytochrome
9208	POR	P450 (cytochrome) oxidoreductase	cytochrome p450 reductase	1.0	ific monooxygenases the cytochrome p 450 enzymes cyps are membrane bound terminal oxidases present mainly in the er as components of a multi enzyme system which also includes fad/fmn containing nadph cytochrome p450 reductase and cytochrome b 5 .
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	they consist of the membrane bound cytochrome b 558 a catalytic gp91 phox subunit also termed nox2 and a p22 phox subunit as well as cytosolic components: p47 phox and p67 phox and the small gtpase rac1 65 .
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67 phox	1.0	they consist of the membrane bound cytochrome b 558 a catalytic gp91 phox subunit also termed nox2 and a p22 phox subunit as well as cytosolic components: p47 phox and p67 phox and the small gtpase rac1 65 .
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	gp91 phox	1.0	they consist of the membrane bound cytochrome b 558 a catalytic gp91 phox subunit also termed nox2 and a p22 phox subunit as well as cytosolic components: p47 phox and p67 phox and the small gtpase rac1 65 .
7427	MT-CYB	mitochondrially encoded cytochrome b	cytochrome b	1.0	they consist of the membrane bound cytochrome b 558 a catalytic gp91 phox subunit also termed nox2 and a p22 phox subunit as well as cytosolic components: p47 phox and p67 phox and the small gtpase rac1 65 .
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	gp91 phox	1.0	this event is followed by translocation of gp91 phox and p47 phox aggregation and activation of nadph oxidases.
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	a crucial event in activation of nox2 is phosphorylation of p47 phox which allows its interaction with p22 phox and binding to cytochrome b 558 65 .
7427	MT-CYB	mitochondrially encoded cytochrome b	cytochrome b	1.0	a crucial event in activation of nox2 is phosphorylation of p47 phox which allows its interaction with p22 phox and binding to cytochrome b 558 65 .
19404	NOXO1	NADPH oxidase organizer 1	nadph oxidase organizer 1	1.0	ntrast to nox1 and nox2 which seem to have structural and functional similarities nox3 is likely to be constitutively active 70 even though its activity may be increased by cytosolic proteins such as nadph oxidase organizer 1 noxo1 an isoform of p47 phox 70 and rac1 71 .
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	it forms a complex with p22 phox that is not modulated by known cytosolic nox regulators such as noxo1 and rac 72 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	loss of mitochondrial integrity is associated with dissipation of _amp_#916;_amp_#x03a8; m and release of apoptogenic proteins such as cytochrome c smac/diablo and aif 77 as a result of increased momp which is regulated by at least two mechanisms 76 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	accordingly it was hypothesized that the closure of vdac rather than its opening leads to cytochrome c release by providing an _amp_#8216;unknown_amp_#8217; signal to another mitochondrial carrier which in turn becomes permeable for cytochrome c 79 80 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	release by providing an _amp_#8216;unknown_amp_#8217; signal to another mitochondrial carrier which in turn becomes permeable for cytochrome c 79 80 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	notably genetic inactivation of vdac did not prevent cytochrome c release in response to oxidative stress increased intracellular ca ++ and tnfr1 signaling 81 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	instead momp is suggested to be mediated by pro apoptotic bcl 2 family members e.g bax bak bad bid acting directly on the outer mitochondrial membrane 82 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	n formation of a signaling complex that forms at the cytoplasmic tail of the receptor that is termed complex i consisting of the adapter tnfri associated death domain protein tradd the protein kinase rip1 and tnf receptor associated factor traf 2 and 5.
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	s complex rapidly signals to activate nf kappab through inhibitor of nf kappab ikappab kinase ikk and mitogen activated protein kinase mapk cascades which regulate other transcription factors such as ap 1 87 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	nf kappab activation inhibits the ability of tnfri to induce apoptosis by augmenting the synthesis of c flip 88 a specific inhibitor of caspase 8/10 activation 89 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	nf kappab activation inhibits the ability of tnfri to induce apoptosis by augmenting the synthesis of c flip 88 a specific inhibitor of caspase 8/10 activation 89 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	following an unknown modification complex i dissociates from the receptor and a cytoplasmic complex of the tradd and traf2 and rip1 is then available to associate with the fas associated death domain protein fadd to form complex ii 86 which can activate caspase 8/10 only in cells that contain low levels of c flip 88 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	radd and traf2 and rip1 is then available to associate with the fas associated death domain protein fadd to form complex ii 86 which can activate caspase 8/10 only in cells that contain low levels of c flip 88 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	s from the receptor and a cytoplasmic complex of the tradd and traf2 and rip1 is then available to associate with the fas associated death domain protein fadd to form complex ii 86 which can activate caspase 8/10 only in cells that contain low levels of c flip 88 .
1500	CASP10	caspase 10, apoptosis-related cysteine peptidase	fas associated death domain protein	1.0	following an unknown modification complex i dissociates from the receptor and a cytoplasmic complex of the tradd and traf2 and rip1 is then available to associate with the fas associated death domain protein fadd to form complex ii 86 which can activate caspase 8/10 only in cells that contain low levels of c flip 88 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	once in the cytosol cathepsins like caspase 8/10 cleave bid 92 induce oligomerization of bax 93 or may interact directly with the mitochondrial outer membrane 94 fig 2 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	rip1 mediated cell death: the bell tolls for mitochondria
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	in addition to being critical for caspase 8 activation 27 96 fig 2 rip1 is needed for ikk and nf kappab activation 97 98 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	in addition to being critical for caspase 8 activation 27 96 fig 2 rip1 is needed for ikk and nf kappab activation 97 98 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	although rip1 is a serine/threonine kinase 99 100 its protein kinase activity is dispensable for nf kappab activation 98 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	caspase 8 can cleave rip1 targeting the aspartic acid at position 324 thereby directing rip1 to induce apoptosis 101 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	caspase 8 can cleave rip1 targeting the aspartic acid at position 324 thereby directing rip1 to induce apoptosis 101 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	as a result rip1 cleavage prevents tnfa induced nf kappab activation and promotes tnfa induced apoptosis through a ripc one of the cleavage products enhanced interaction between tradd fadd and caspase 8 101 fig 2 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	as a result rip1 cleavage prevents tnfa induced nf kappab activation and promotes tnfa induced apoptosis through a ripc one of the cleavage products enhanced interaction between tradd fadd and caspase 8 101 fig 2 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	rip1 cleavage was also detected after activation of other drs 3 101 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	rip1 kinase activity however may be required for dr induced non apoptotic cell death 102 which is accompanied with increased ros levels 13 14 85 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	however this has not been fully validated and rip1 substrates involved in cell death are yet to be identified.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	overexpression of either wildtype rip1 or a rip1 mutant lacking the kinase domain induced cell death 103 ; however the rip1 kinase domain seems to be involved in c jun n terminal protein kinase jnk activation 27 which may facilitate momp upon tnfri mediated apoptosis through promotion of c flip degradation 88 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	cell death 103 ; however the rip1 kinase domain seems to be involved in c jun n terminal protein kinase jnk activation 27 which may facilitate momp upon tnfri mediated apoptosis through promotion of c flip degradation 88 .
6204	JUN	jun oncogene	c jun	1.0	overexpression of either wildtype rip1 or a rip1 mutant lacking the kinase domain induced cell death 103 ; however the rip1 kinase domain seems to be involved in c jun n terminal protein kinase jnk activation 27 which may facilitate momp upon tnfri mediated apoptosis through promotion of c flip degradation 88 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	tnfa is still able to activate jnk in rip1 deficient cells 104 even though this activation is not as strong as in wildtype cells 104 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	furthermore rip1 may be involved in activation of caspase 2 105 and akt 1 106 and their activity might be crucial in modulation of mitochondrial function 107 108 .
1503	CASP2	caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2)	caspase 2	1.0	furthermore rip1 may be involved in activation of caspase 2 105 and akt 1 106 and their activity might be crucial in modulation of mitochondrial function 107 108 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	in monocytic cells tnfa induced rip1 dependent inhibition of ant conducted adp transport into mitochondria led to progressively reduced atp levels vacuolization of organelles and disintegration of the plasma membrane with only negligibl
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	cyclophilin d	1.0	tnfa induced dissociation of mitochondrial matrix peptidyl prolyl isomerase 109 cyclophilin d from ant.
8988	PIN1	peptidylprolyl cis/trans isomerase, NIMA-interacting 1	prolyl isomerase	1.0	tnfa induced dissociation of mitochondrial matrix peptidyl prolyl isomerase 109 cyclophilin d from ant.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	however because anti oxidants failed to alter rip1 mediated cell death 85 a role for other ros cannot be completely excluded.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	because rip1 trafficked to mitochondria after tnfa stimulation of cells cytochrome c release was not observed and caspase 8 seems to be dispensable 85 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	because rip1 trafficked to mitochondria after tnfa stimulation of cells cytochrome c release was not observed and caspase 8 seems to be dispensable 85 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	because rip1 trafficked to mitochondria after tnfa stimulation of cells cytochrome c release was not observed and caspase 8 seems to be dispensable 85 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	it was therefore proposed that rip1 may initiate a new mitochondrial pathway that is not dependent on complex ii and fadd:caspase 8 interaction 85 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	our recent unpublished data suggest that traffic and association of rip1 with mitochondria may be modulated by nf kappab signaling fig 3 .
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	nonetheless the mechanisms by which rip1 affects the ant cyclophilin d complex as well as the mitochondrial target of rip1 are yet to be identified.
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	cyclophilin d	1.0	nonetheless the mechanisms by which rip1 affects the ant cyclophilin d complex as well as the mitochondrial target of rip1 are yet to be identified.
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	cyclophilin d	1.0	the role of cyclophilin d in adaptation of mitochondria to abnormal intracellular homeostasis has recently been clarified 83 111 .
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	cyclophilin d	1.0	cyclophilin d knockout mice showed no abnormality but demonstrated a high level of resistance to ischemia/reperfusion induced cardiac injury 83 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	cyclophilin d null cells are as sensitive as wildtype cells to tnfa or pro apoptotic bcl 2 family member induced cell death 111 but exhibit increased sensitivity to h 2 o 2 and excessive intracellular ca ++ 111 .
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	cyclophilin d	1.0	cyclophilin d null cells are as sensitive as wildtype cells to tnfa or pro apoptotic bcl 2 family member induced cell death 111 but exhibit increased sensitivity to h 2 o 2 and excessive intracellular ca ++ 111 .
9257	PPID	peptidylprolyl isomerase D (cyclophilin D)	cyclophilin d	1.0	notably in breast ovarian and uterine cancers 112 viral cardiomyopathy 113 and certain myopathies 114 altered expression or function of either ant or cyclophilin d is observed.
5992	IL1B	interleukin 1, beta	il 1b	1.0	unlike tnfa mediated nf kappab activation 115 il 1b mediated activation of nf kappab was suggested to require ros production by nox2 116 .
6025	IL8	interleukin 8	il 8	1.0	tlr4 may use myd88 for activation of nox 118 and ros production was proposed to be involved in tlr4 induced nf kappab activation 119 120 and il 8 production 120 .
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	it was proposed that jnk activation somehow promotes processing of the bh3 domain protein bid to the pro apoptotic cleavage product jbid 128 which akin to caspase 8 cleaved bid tbid 129 allows tnfa induced apoptosis to proceed fig 2 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	by examining the effect of jnk1 on proteins known to be involved in tnfri signaling we found that jnk activity controls tnfa induced death through the induced proteasomal degradation of c flip 88 .
21148	RNF123	ring finger protein 123	ubiquitin ligase	1.0	jnk1 however does not phosphorylate c flip itself and instead leads to phosphorylation dependent activation of the ubiquitin ligase itch 88 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	jnk1 however does not phosphorylate c flip itself and instead leads to phosphorylation dependent activation of the ubiquitin ligase itch 88 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	itch specifically interacts with the long isoform of c flip c flip l to promote its polyubiquitination and proteasomal degradation.
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	thus whereas nf kappab activation prevents tnfa induced cell death by increasing the intracellular concentration of c flip l 88 89 prolonged jnk activation promotes tnfa induced death by decreasing the concentration of c flip l 88 an inhibitor of tnfri induced cell death 131 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	l 88 89 prolonged jnk activation promotes tnfa induced death by decreasing the concentration of c flip l 88 an inhibitor of tnfri induced cell death 131 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	in addition to elevating c flip l concentrations through transcriptional activation of the c flip gene nf kappab activation maintains high levels of c flip l by preventing persistent jnk activation 88 .
992	BCL2L1	BCL2-like 1	bcl x	1.0	currently it is known that nf kappab is a transcriptional activator of many anti apoptotic genes including c flip c iap 1 c iap 2 x chromosome linked iap xiap bcl x l a1/bfl1 gadd 45b and sod2 126 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	currently it is known that nf kappab is a transcriptional activator of many anti apoptotic genes including c flip c iap 1 c iap 2 x chromosome linked iap xiap bcl x l a1/bfl1 gadd 45b and sod2 126 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	as documented above one of the most critical nf kappab activated anti apoptotic molecules in the contest of tnfri induced apoptosis is c flip 131 .
8584	SERPINB2	serpin peptidase inhibitor, clade B (ovalbumin), member 2	pai 2	1.0	however other nf kappab target genes for instance a1/bfl1 and pai 2 are more critical for prevention of apoptosis in response to activation of tlr4 in macrophages 144 .
992	BCL2L1	BCL2-like 1	bcl xl	1.0	these proteins are anti apoptotic members of the bcl2 family: mcl 1 bcl xl and a1/bfl 1.
990	BCL2	B-cell CLL/lymphoma 2	bcl2	1.0	these proteins are anti apoptotic members of the bcl2 family: mcl 1 bcl xl and a1/bfl 1.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	sion of bcl xl however does not block tnfa induced cell death momp and loss of _amp_#916;_amp_#x03a8; m 148 suggesting that tnfa also kills cells via a pathway that is not inhibited by anti apoptotic bcl 2 proteins 148 .
992	BCL2L1	BCL2-like 1	bcl xl	1.0	overexpression of bcl xl however does not block tnfa induced cell death momp and loss of _amp_#916;_amp_#x03a8; m 148 suggesting that tnfa also kills cells via a pathway that is not inhibited by anti apoptotic bcl 2 proteins
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	although several nf kappab regulated genes such as c iap1 c iap2 a20 and c flip were suggested to mediate the inhibitory effect on complex ii and/or its components 89 140 149 151 the precise mechanism remains to be clarified.
2527	CTSB	cathepsin B	cathepsin b	1.0	the nf kappab dependent upregulation of serine protease inhibitor 2a a potent inhibitor of cathepsin b was shown to provide partial protection from tnfa induced apoptosis 152 .
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	c flip	1.0	however the relationships between this pathway and the main tnfa induced death pathway which is inhibited by c flip at the level of caspase 8/10 are not clear.
1509	CASP8	caspase 8, apoptosis-related cysteine peptidase	caspase 8	1.0	however the relationships between this pathway and the main tnfa induced death pathway which is inhibited by c flip at the level of caspase 8/10 are not clear.
1516	CAT	catalase	catalase	1.0	unlike other anti oxidant scavenger enzymes such as gpx and catalase sod2 is almost exclusively located in the mitochondrial matrix 46 fig 1 .
2726	DDIT3	DNA-damage-inducible transcript 3	growth arrest and dna damage inducible	1.0	however it was also suggested by several groups that the molecular link between nf kappab and jnk inhibition is provided by anti apoptotic nf kappab regulated genes such as xiap 125 and growth arrest and dna damage inducible 45b gadd45 b 123 .
2434	CSF2	colony stimulating factor 2 (granulocyte-macrophage)	gm csf	1.0	erk and p38 mapk whose activity is stimulated by tnfa were found to phosphorylate ser345 of p47phox in response to gm csf and tnf respectively.
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	neutrophil cytosolic factor 1	1.0	however decreased ability to produce ros because of polymorphisms in the ncf1 locus which encodes neutrophil cytosolic factor 1 was reported to increase susceptibility to autoimmunity and arthritis 168 169 and oxidative burst inducing agents prevent experimental arthritis 170 .
5992	IL1B	interleukin 1, beta	il 1b	1.0	in t1d immune cells are activated and express proinflammatory cytokines such as tnfa il 1b and infg 173 .
6081	INS	insulin	insulin	1.0	tnfa mediated insulin resistance requires increased ros accumulation 179 consistent with its jnk dependence.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	conclusion: puzzles of the day rip1 association with mitochondria the mechanism by which dr activation may affect mitochondrial function may to be only the tip of the iceberg.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	furthermore the exact role played by rip1 in mitochondria is far from clear.
10019	RIPK1	receptor (TNFRSF)-interacting serine-threonine kinase 1	rip1	1.0	in addition the potential role of nf kappab on rip1 association with mitochondria and how exactly nf kappab prevent formation of complex ii need to be elucidated.