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PMID	11679167 ( )
Title	Oxidative stress and signal transduction in Saccharomyces cerevisiae: insights into ageing, apoptosis and diseases.
Abstract	In yeast, as in higher eukaryotes, reactive oxygen species are produced as normal by-products of cellular metabolism. Under physiological conditions, the cell defence mechanisms are able to avoid molecular damages. This balance is disturbed when yeast cells are exposed to diverse environmental stress conditions, such as the presence of oxidants, heat shock, ethanol and metal ions. The increased production of reactive oxygen species is sensed by the cell, leading to the induction of defence mechanisms - the oxidative stress response. The present review discusses the mechanisms by which reactive oxygen species are sensed and the signalling pathways that are coupled with changes in genomic expression programs. Yeast has been used as an eukaryotic cell system to characterise the molecular mechanisms underlying the oxidative stress response. Furthermore, yeast has been utilised to elucidate the role of oxidative stress in ageing, apoptosis, and diseases, such as familial amyotrophic lateral sclerosis and Friedreich's ataxia. Microrganismos, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.

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
12435	TXN	thioredoxin	13	thioredoxin \| trx \|
990	BCL2	B-cell CLL/lymphoma 2	11	Bcl-2 \| bcl 2 \|
11180	SOD2	superoxide dismutase 2, mitochondrial	10	MnSOD \| mn superoxide dismutase \| SOD2 \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	10	SOD1 \| SODs \| SOD \| superoxide dismutase \|
3951	FXN	frataxin	7	FRDA \| frataxin \|
20374	GSX1	GS homeobox 1	6	gsh1 \| GSH1 \|
9391	PRKAR2A	protein kinase, cAMP-dependent, regulatory, type II, alpha	5	protein kinase a \|
19986	CYCS	cytochrome c, somatic	5	cytochrome c \|
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	5	glyceraldehyde 3 phosphate dehydrogenase \|
118	ACO2	aconitase 2, mitochondrial	4	aconitase \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	3	Akt \| protein kinase b \|
959	BAX	BCL2-associated X protein	3	BAX \|
1516	CAT	catalase	3	catalase \|
17169	PRDX4	peroxiredoxin 4	3	thioredoxin peroxidase \|
4092	GAD1	glutamate decarboxylase 1 (brain, 67kDa)	2	GAD1 \| Gad1 \|
4057	G6PD	glucose-6-phosphate dehydrogenase	2	glucose 6 phosphate dehydrogenase \|
24959	GSX2	GS homeobox 2	2	GSH2 \|
9827	RAD9A	RAD9 homolog A (S. pombe)	2	RAD9-dependent \| RAD9-independent \|
992	BCL2L1	BCL2-like 1	2	bcl x \| Bcl-x \|
4330	GLRX	glutaredoxin (thioltransferase)	2	glutaredoxin \| grx \|
48	ABCB7	ATP-binding cassette, sub-family B (MDR/TAP), member 7	2	Atm1p \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	2	ap 1 \| AP-1 \|
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	2	ANT \|
2244	COQ7	coenzyme Q7 homolog, ubiquinone (yeast)	2	coenzyme q \|
7804	NFYA	nuclear transcription factor Y, alpha	2	Hap2 \|
12343	TRNAR1	transfer RNA arginine 1 (anticodon UCU)	1	TRR1 \|
14133	SEPX1	selenoprotein X, 1	1	methionine sulfoxide reductase \|
6081	INS	insulin	1	insulin \|
12024	CRISP2	cysteine-rich secretory protein 2	1	TPX1 \|
10417	RPS27A	ribosomal protein S27a	1	ubiquitin \|
5232	HSPA1A	heat shock 70kDa protein 1A	1	HSP \|
17772	TXN2	thioredoxin 2	1	TRX2 \|
412	ALDH9A1	aldehyde dehydrogenase 9 family, member A1	1	aldehyde dehydrogenase \|
30213	ATP13A2	ATPase type 13A2	1	putative atpase \|
4455	GPD1	glycerol-3-phosphate dehydrogenase 1 (soluble)	1	Gpd1 \|
19737	TENC1	tensin like C1 domain containing phosphatase (tensin 2)	1	putative protein tyrosine phosphatase \|
25806	GSTCD	glutathione S-transferase, C-terminal domain containing	1	glutathione s transferase \|
16554	SLC25A6P1	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6, pseudogene 1	1	adenine nucleotide translocator \|
1260	C21orf2	chromosome 21 open reading frame 2	1	nuclear encoded mitochondrial protein \|
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	1	COX \|
949	BAK1	BCL2-antagonist/killer 1	1	Bak \|
34	ABCA4	ATP-binding cassette, sub-family A (ABC1), member 4	1	atp binding cassette transporter \|
12015	TPO	thyroid peroxidase	1	mTpx \|
21285	ADCY10	adenylate cyclase 10 (soluble)	1	adenylate cyclase \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
3951	FXN	frataxin	FRDA	2.0	in diseases related to oxidative stress such as ALS or FRDA (see see Sections 4.3 and 4.4
118	ACO2	aconitase 2, mitochondrial	aconitase	1.3	oxidise 4Fe_amp_#x2013 4S clusters in enzymes such as the mitochondrial aconitase (citric citric acid cycle homoaconitase (lysine lysine biosynthesis and isopropyl
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	2.4	superoxide dismutases (either either the cytosolic CuZnSOD or the mitochondrial MnSOD or both ( Srinivasan et al. 2000 De Freitas et
118	ACO2	aconitase 2, mitochondrial	aconitase	1.3	The inactivation of mitochondrial enzymes (aconitase) aconitase results in an impaired respiratory activity that limits the capacity
20374	GSX1	GS homeobox 1	GSH1	1.5	The disruption of GSH1 gene encoding the rate-limiting enzyme of glutathione biosynthesis increases hydrogen
20374	GSX1	GS homeobox 1	gsh1	1.5	its role in oxidative stress resistance as suppressors of the gsh1 mutation that decreased the rate of generation of petites did
48	ABCB7	ATP-binding cassette, sub-family B (MDR/TAP), member 7	Atm1p	1.9	Atm1p an ATP-binding cassette transporter that controls iron homeostasis within the
48	ABCB7	ATP-binding cassette, sub-family B (MDR/TAP), member 7	Atm1p	1.9	Loss of Atm1p increases free iron levels and leads to the accumulation of
9827	RAD9A	RAD9 homolog A (S. pombe)	RAD9-dependent	1.0	the level of cell cycle arrest hydrogen peroxide induces a RAD9-dependent arrest in G 2 while superoxide causes a RAD9-independent arrest
9827	RAD9A	RAD9 homolog A (S. pombe)	RAD9-independent	1.0	a RAD9-dependent arrest in G 2 while superoxide causes a RAD9-independent arrest in G 1 ( Flattery-O'Brien and Dawes 1998
20374	GSX1	GS homeobox 1	GSH1	1.5	is also correlated with glutathione levels as the expression of GSH1 and GSH2 genes coding for the two enzymes involved in
24959	GSX2	GS homeobox 2	GSH2	1.5	is also correlated with glutathione levels as the expression of GSH1 and GSH2 genes coding for the two enzymes involved in
24959	GSX2	GS homeobox 2	GSH2	1.5	correlated with glutathione levels as the expression of GSH1 and GSH2 genes coding for the two enzymes involved in glutathione synthesis
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	2.4	such as the increase of the mitochondrial superoxide dismutase (MnSOD) MnSOD activity by ethanol the high ethanol sensitivity of S cerevisiae
11180	SOD2	superoxide dismutase 2, mitochondrial	MnSOD	2.4	the high ethanol sensitivity of S cerevisiae cells deficient in MnSOD ( Costa and Costa and the induction of CTT1 gene
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SODs	1.9	glucose consuming cultures some of the antioxidant defences such as SODs catalases and peroxidases are present at a very low level
7804	NFYA	nuclear transcription factor Y, alpha	Hap2	1.6	sensing of oxygen and different trans-acting factors _amp_#x2013 Hap1p Hap2/3/4/5p Hap2 3 4 5p and Rox1p are involved in this gene
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.7	in oxidative stress only two genes are under Hap1p regulation SOD2 and CTT1
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.7	Hap1p is a positive regulator of SOD2 promoter in glucose growing cells ensuring a basel level of
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COX	1.4	of anoxia on the expression of the nuclear aerobic genes COX indicated the existence of a signalling pathway from the mitochondria
4330	GLRX	glutaredoxin (thioltransferase)	grx	0.3	sod 1_amp_#x394 sod 2_amp_#x394 glutathione ( gsh 1_amp_#x394 glutaredoxin ( grx 5_amp_#x394 ubiquinol ( coq 3_amp_#x394 or poliamines ( spe 2_amp_#x394
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.7	regulates the transcriptional activation of the antioxidant genes such as SOD2 (mitochondrial mitochondrial superoxide dismutase CTA1 (peroxisomal peroxisomal catalase CTT1 (cytosolic
7804	NFYA	nuclear transcription factor Y, alpha	Hap2	1.6	The heteromeric complex Hap2/3/4/5p Hap2 3 4 5p binds CCAAT sequences and is responsible for
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.7	induction of several genes important for respiration as well as SOD2 and UBI4 ( Pinkham et al. 1997
11180	SOD2	superoxide dismutase 2, mitochondrial	SOD2	2.7	growth in a non-fermentable carbon source the transcriptional activation of SOD2 and CTT1 genes is also regulated by Msn2p and Msn4p
12015	TPO	thyroid peroxidase	mTpx	0.3	Other antioxidant defences such as Ccp1p Cta1p Cup1p Gpx1p and mTpx are induced during respiratory growth however the regulatory mechanisms remain
4092	GAD1	glutamate decarboxylase 1 (brain, 67kDa)	GAD1	1.2	and the loss/overexpression loss overexpression of glutamate decarboxylase gene ( GAD1 decreases/increases decreases increases hydrogen peroxide resistance ( Coleman et al.
12435	TXN	thioredoxin	trx	1.0	Indeed Yap1p is constitutively active in thioredoxin deficient mutants ( trx 1_amp_#x394 trx 2_amp_#x394 ( Izawa et al. 1999 and the
12435	TXN	thioredoxin	trx	1.0	is constitutively active in thioredoxin deficient mutants ( trx 1_amp_#x394 trx 2_amp_#x394 ( Izawa et al. 1999 and the whole genome
17772	TXN2	thioredoxin 2	TRX2	1.3	thioredoxin peroxidase Tpx1p is essential for the transcriptional activation of TRX2 and TRR1 genes ( Ross et al. 2000
12343	TRNAR1	transfer RNA arginine 1 (anticodon UCU)	TRR1	2.1	Tpx1p is essential for the transcriptional activation of TRX2 and TRR1 genes ( Ross et al. 2000
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	AP-1	1.0	Interestingly the yeast AP-1 family (Yap1p) Yap1p of proteins are involved in the sensing
12024	CRISP2	cysteine-rich secretory protein 2	TPX1	1.6	Indeed the induction of TPX1 (thioredoxin thioredoxin peroxidase gene is Skn7p- and Yap1p-dependent and is
118	ACO2	aconitase 2, mitochondrial	aconitase	1.3	destroy the 4Fe_amp_#x2013 4S clusters of mitochondrial enzymes (e.g., e.g. aconitase leading to an impaired respiratory activity
118	ACO2	aconitase 2, mitochondrial	aconitase	1.3	a delay in the reversible inactivation of the superoxide-sensitive enzyme aconitase suggesting that the extension of life-span is associated with the
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.0	is an homologue of the mammalian protein kinase B/Akt, B Akt which is involved in insulin signalling apoptosis and cellular proliferation
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.0	Sch9/Rim15 Sch9 Rim15 and the C elegans DAF-2/AGE-1/Akt/DAF16 DAF-2 AGE-1 Akt DAF16 pathways play similar roles in regulating ageing and stress
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	2.6	been identified as being major regulators of apoptosis including the Bcl-2 family and caspases
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	2.6	The Bcl-2 family of proteins consist of anti-apoptotic proteins such as Bcl-2
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	2.6	Bcl-2 family of proteins consist of anti-apoptotic proteins such as Bcl-2 and Bcl-x(L), Bcl-x L and pro-apoptotic proteins such as Bax
992	BCL2L1	BCL2-like 1	Bcl-x	1.0	proteins consist of anti-apoptotic proteins such as Bcl-2 and Bcl-x(L), Bcl-x L and pro-apoptotic proteins such as Bax and Bak (
949	BAK1	BCL2-antagonist/killer 1	Bak	0.0	Bcl-x(L), Bcl-x L and pro-apoptotic proteins such as Bax and Bak ( Gross et al. 1999
959	BAX	BCL2-associated X protein	BAX	0.3	Indeed the expression of BAX stimulates the production of reactive oxygen species ( Madeo et
959	BAX	BCL2-associated X protein	BAX	0.3	apoptosis ( Madeo et al. 1999 (ii) ii expression of BAX decreases the intracellular levels of glutathione decreases the mitochondrial membrane
959	BAX	BCL2-associated X protein	BAX	0.3	S-transferase/peroxidase S-transferase peroxidase ( Kampranis et al. 2000 (iii) iii BAX lethality is higher under respiratory conditions and is suppressed in
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	2.6	lacking superoxide dismutase is extended by overexpressing the anti-apoptotic protein Bcl-2 ( Longo et al. 1999
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	2.6	The regulatory role of the Bcl-2 members e.g. depends on their ability to regulate the mitochondrial
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	2.6	In yeast Bcl-2 proteins interact with the voltage-dependent anion channel (VDAC) VDAC and
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	anion channel (VDAC) VDAC and the adenine nucleotide translocator (ANT), ANT and these proteins are components of the mitochondrial permeability transition
10990	SLC25A4	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4	ANT	0.6	However ANT is not essential for Bax-induced cytochrome c release from the
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD	1.9	been utilised for ALS research on clarifying the role of SOD mutations
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.9	the use of S cerevisiae in elucidating the mechanism of SOD1 mediated disease
3951	FXN	frataxin	FRDA	2.0	Friedreich's ataxia (FRDA) FRDA
4455	GPD1	glycerol-3-phosphate dehydrogenase 1 (soluble)	Gpd1	0.3	Zwf1 glucose-6-phosphate dehydrogenase Gpd1 glycerol phosphate dehydrogenase Gpp2 glycerol phosphate phosphatase YBR149W glycerol dehydrogenase
4092	GAD1	glutamate decarboxylase 1 (brain, 67kDa)	Gad1	1.2	Gpp2 glycerol phosphate phosphatase YBR149W glycerol dehydrogenase Dak1 dihydroxyacetone kinase Gad1 glutamate decarboxylase Uga5 succinate semialdehyde dehydrogenase
5232	HSPA1A	heat shock 70kDa protein 1A	HSP	0.9	the Hsf1p increase the expression of heat shock proteins (HSP) HSP and chaperones Yap1p and Skn7p upregulate antioxidant genes
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	the importance of this protective mechanism is illustrated by tdh3p a glyceraldehyde 3 phosphate dehydrogenase isoform.
14133	SEPX1	selenoprotein X, 1	methionine sulfoxide reductase	1.0	methionine sulfoxide reductase is able to repair mildly oxidised proteins by reducing methionine sulfoxide to methionine.
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	it was recently shown that hydrogen peroxide induced protein carbonylation is specific and glyceraldehyde 3 phosphate dehydrogenase and mitochondrial enzymes are the major targets inactivated cabiscol et al. 2000 .
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	the inactivation of glyceraldehyde 3 phosphate dehydrogenase may contribute to cellular protection as it increases the levels of glucose 6 phosphate to be used in the pentose phosphate pathway in order to increase the production of nadph see section 3.4 .
10417	RPS27A	ribosomal protein S27a	ubiquitin	1.0	in s. cerevisiae several components of the ubiquitin 26s proteasome pathway and vacuolar proteases are induced by hydrogen peroxide godon et al. 1998 ; lee et al. 1999 which is consistent with the involvement of these proteolytic pathways in the degrad
20374	GSX1	GS homeobox 1	gsh1	1.0	the disruption of gsh1 gene encoding the rate limiting enzyme of glutathione biosynthesis increases hydrogen peroxide sensitivity but also leads to a high frequency of petite respiration deficient cell generation.
20374	GSX1	GS homeobox 1	gsh1	1.0	the function of glutathione in the protection of the mtdna is independent of its role in oxidative stress resistance as suppressors of the gsh1 mutation that decreased the rate of generation of petites did not increase hydrogen peroxide resistance of gsh 1_amp_#x394; cells lee et al. 2001 .
34	ABCA4	ATP-binding cassette, sub-family A (ABC1), member 4	atp binding cassette transporter	1.0	atm1p an atp binding cassette transporter that controls iron homeostasis within the yeast mitochondria is also important for mtdna integrity.
2244	COQ7	coenzyme Q7 homolog, ubiquinone (yeast)	coenzyme q	1.0	the toxicity of lipid hydroperoxides has been associated to a decrease of coenzyme q and glutathione levels.
2244	COQ7	coenzyme Q7 homolog, ubiquinone (yeast)	coenzyme q	1.0	coenzyme q as well as vitamin e protect cells by reducing lipid peroxyl radicals and therefore by inhibiting the propagation of lipid peroxidation do et al. 1996 .
19737	TENC1	tensin like C1 domain containing phosphatase (tensin 2)	putative protein tyrosine phosphatase	1.0	it was recently shown that the inhibition of yeast growth by linoleic acid hydroperoxide requires a putative protein tyrosine phosphatase oca1p of unknown function.
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	the association of heat shock and oxidative stress is further supported by the data revealing that the superoxide dismutase genes are upregulated by heat shock costa et al. 1997 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	in agreement s. cerevisiae mutants deficient in antioxidant defences such as catalase superoxide dismutase and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe heat shock davidson et al. 1996 .
1516	CAT	catalase	catalase	1.0	in agreement s. cerevisiae mutants deficient in antioxidant defences such as catalase superoxide dismutase and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe
1516	CAT	catalase	catalase	1.0	superoxide dismutase and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe heat shock davidson et al. 1996 .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	in agreement s. cerevisiae mutants deficient in antioxidant defences such as catalase superoxide dismutase and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe heat shock davidson e
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	and cytochrome c peroxidase are sensitive to a lethal heat shock and the overexpression of genes encoding catalase and superoxide dismutase increase the resistance to the severe heat shock davidson et al. 1996 .
20374	GSX1	GS homeobox 1	gsh1	1.0	the oxygen heat shock association is also correlated with glutathione levels as the expression of gsh1 and gsh2 genes coding for the two enzymes involved in glutathione synthesis is induced by a sublethal heat shock under aerobic but not anaerobic conditions sugiyama et al. 2000a .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	the link between ethanol and oxidative stress was revealed by different experimental evidences such as the increase of the mitochondrial superoxide dismutase mnsod activity by ethanol the high ethanol sensitivity of s. cerevisiae cells deficient in mnsod costa and costa and the induction of ctt1 gene upon ethanol stress schuller et al. 1994 .
4330	GLRX	glutaredoxin (thioltransferase)	glutaredoxin	1.0	owth is highlighted by a significant decrease in the growth rate of cells deficient in antioxidant defences namely superoxide dismutases sod 1_amp_#x394; sod 2_amp_#x394; glutathione gsh 1_amp_#x394; glutaredoxin grx 5_amp_#x394; ubiquinol coq 3_amp_#x394; or poliamines spe 2_amp_#x394; moradas ferreira and costa 2000 .
9391	PRKAR2A	protein kinase, cAMP-dependent, regulatory, type II, alpha	protein kinase a	1.0	in glucose consuming cells the high activity of protein kinase a represses gene transcription mediated by these factors.
1516	CAT	catalase	catalase	1.0	hap1p regulates the transcriptional activation of the antioxidant genes such as sod2 mitochondrial superoxide dismutase cta1 peroxisomal catalase ctt1 cytosolic catalase and ubi4 polyubiquitin .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	hap1p regulates the transcriptional activation of the antioxidant genes such as sod2 mitochondrial superoxide dismutase cta1 peroxisomal catalase ctt1 cytosolic catalase and ubi4 polyubiquitin .
4057	G6PD	glucose-6-phosphate dehydrogenase	glucose 6 phosphate dehydrogenase	1.0	for example the increasing requirement of nadph is met by the increase of glucose 6 phosphate utilisation by the pentose phosphate pathway as the activity of glucose 6 phosphate dehydrogenase zwf1p is induced by hydrogen peroxide.
12435	TXN	thioredoxin	thioredoxin	1.0	indeed the nadph is essential for the glutathione and the thioredoxin antioxidant systems which play a key role in maintaining a reduced intracellular state in the cells challenged by an oxidative stress fig 5 kuge and jones 1994 ; izawa et al. 1995 ; morgan et al. 199
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	i the glycolytic flux is inhibited: genes coding for glycolytic enzymes are downregulated and glyceraldehyde 3 phosphate dehydrogenase is oxidatively inactivated see section 2.1 .
4141	GAPDH	glyceraldehyde-3-phosphate dehydrogenase	glyceraldehyde 3 phosphate dehydrogenase	1.0	the inhibition of the glycolytic pathway at the step catalysed by glyceraldehyde 3 phosphate dehydrogenase increases the pool of dihydroxyacetone phosphate available for the glycerol cycle godon et al. 1998 .
412	ALDH9A1	aldehyde dehydrogenase 9 family, member A1	aldehyde dehydrogenase	1.0	iii the glutamate catabolic pathway is upregulated: the expression of succinate semi aldehyde dehydrogenase gene uga5 is induced and the loss/overexpression of glutamate decarboxylase gene gad1 decreases/increases hydrogen peroxide resistance coleman et al. 2001 .
9391	PRKAR2A	protein kinase, cAMP-dependent, regulatory, type II, alpha	protein kinase a	1.0	under non stress conditions these factors are negatively regulated by the ras/protein kinase a pathway which is activated by glucose and promotes cellular growth fig 3 .
9391	PRKAR2A	protein kinase, cAMP-dependent, regulatory, type II, alpha	protein kinase a	1.0	under stress conditions the ras/protein kinase a pathway is inhibited and the different transcription factors are activated by specific signal transduction pathways.
9391	PRKAR2A	protein kinase, cAMP-dependent, regulatory, type II, alpha	protein kinase a	1.0	yap1p also upregulates the rpi1 gene which codes for protein that represses the ras/protein kinase a pathway dumond et al. 2000 .
17169	PRDX4	peroxiredoxin 4	thioredoxin peroxidase	1.0	it was recently shown that the thioredoxin system consisting of thioredoxin thioredoxin reductase and thioredoxin peroxidase plays a key role in regulating the yap1p dependent stress response.
12435	TXN	thioredoxin	thioredoxin	1.0	indeed yap1p is constitutively active in thioredoxin deficient mutants trx 1_amp_#x394; trx 2_amp_#x394; izawa et al. 1999 and the whole genome analysis of gene expression showed that 70% of the yap1p targets are upregulated in mutants lacking thioredo
12435	TXN	thioredoxin	thioredoxin	1.0	deficient mutants trx 1_amp_#x394; trx 2_amp_#x394; izawa et al. 1999 and the whole genome analysis of gene expression showed that 70% of the yap1p targets are upregulated in mutants lacking thioredoxin reductase trr 1_amp_#x394; under non stress conditions carmel harel et al. 2001 .
17169	PRDX4	peroxiredoxin 4	thioredoxin peroxidase	1.0	in addition the thioredoxin peroxidase tpx1p is essential for the transcriptional activation of trx2 and trr1 genes ross et al. 2000 .
12435	TXN	thioredoxin	thioredoxin	1.0	as yap1p/skn7p mediates the upregulation of thioredoxin system these results indicate that yap1p function is regulated by a feedback mechanism.
12435	TXN	thioredoxin	thioredoxin	1.0	the reduction of yap1p disulphide bonds by the thioredoxin system exposes the nuclear export signals and crm1p exports yap1p back to the cytoplasm.
12435	TXN	thioredoxin	thioredoxin	1.0	these results suggest that the effects of hydrogen peroxide endogenously produced or added are stronger in cells lacking thioredoxin reductase probably due to a decreased capacity to eliminate the oxidant and/or to reduce yap1p disulphide bonds.
12435	TXN	thioredoxin	thioredoxin	1.0	despite the increased levels of antioxidant defences and other stress proteins the trr 1_amp_#x394; mutants are hypersensitive to hydrogen peroxide indicating that the thioredoxin system plays a critical role in the detoxification of hydrogen peroxide.
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	interestingly the yeast ap 1 family yap1p of proteins are involved in the sensing of reactive oxygen species in the different yeasts toone et al. 2001 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	the activation of these factors requires a functional mitochondria and the activity of cytochrome c peroxidase ccp1p .
17169	PRDX4	peroxiredoxin 4	thioredoxin peroxidase	1.0	indeed the induction of tpx1 thioredoxin peroxidase gene is skn7p and yap1p dependent and is lower in respiration deficient mutants and ccp 1_amp_#x394; cells charizanis et al. 1999 .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	the accumulation of oxidised proteins carbonyls and mixed disulphides and the increased production of reactive oxygen species concomitant with a depletion of antioxidant defences glutathione and superoxide dismutase seem to be key factors in ageing and cell death.
11180	SOD2	superoxide dismutase 2, mitochondrial	mn superoxide dismutase	1.0	ted to respiratory growth conditions which display high levels of antioxidant defences maclean et al. 2001 and by the decreased life span observed in mutants deficient in cuzn superoxide dismutase or mn superoxide dismutase longo et al. 1999 .
11180	SOD2	superoxide dismutase 2, mitochondrial	mn superoxide dismutase	1.0	the deficiency in mn superoxide dismutase leads to the accumulation of superoxide radicals which destroy the 4fe_amp_#x2013;4s clusters of mitochondrial enzymes e.g. aconitase leading to an impaired respiratory activity.
21285	ADCY10	adenylate cyclase 10 (soluble)	adenylate cyclase	1.0	in agreement mutations in adenylate cyclase extend life span by a msn2/4p dependent mechanism.
6081	INS	insulin	insulin	1.0	sch9p is an homologue of the mammalian protein kinase b/akt which is involved in insulin signalling apoptosis and cellular proliferation and functions in a pathway that regulates ageing and stress resistance paradis et al. 1999 .
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	protein kinase b	1.0	sch9p is an homologue of the mammalian protein kinase b/akt which is involved in insulin signalling apoptosis and cellular proliferation and functions in a pathway that regulates ageing and stress resistance paradis et al. 1999 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	several proteins have been identified as being major regulators of apoptosis including the bcl 2 family and caspases.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	the bcl 2 family of proteins consist of anti apoptotic proteins such as bcl 2 and bcl x l and pro apoptotic proteins such as bax and bak gross et al. 1999 .
992	BCL2L1	BCL2-like 1	bcl x	1.0	the bcl 2 family of proteins consist of anti apoptotic proteins such as bcl 2 and bcl x l and pro apoptotic proteins such as bax and bak gross et al. 1999 .
30213	ATP13A2	ATPase type 13A2	putative atpase	1.0	the mutation of the yeast cdc48 gene which codes for a putative atpase homologous to the mammalian anti apoptotic valosine containing protein vcp shirogane et al. 1999 also induces both apoptosis and the accumulation of reactive oxygen species madeo et al. 1997 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	on dna strand breaks and plasma membrane inversion laun et al. 2001 ; v the life span of non dividing yeast cells lacking superoxide dismutase is extended by overexpressing the anti apoptotic protein bcl 2 longo et al. 1999 .
25806	GSTCD	glutathione S-transferase, C-terminal domain containing	glutathione s transferase	1.0	cellular levels of glutathione decreases the mitochondrial membrane potential and affects the intracellular redox potential and these effects are reverted by expression of a plant antioxidant defence glutathione s transferase/peroxidase kampranis et al. 2000 ; iii bax lethality is higher under respiratory conditions and is suppressed in respiration deficient mutants and by inhibition of the f 0 f 1 atpase/h + pump with ol
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	both oxidative stress see above and apoptosis including chromatin fragmentation dna strand breaks and plasma membrane inversion laun et al. 2001 ; v the life span of non dividing yeast cells lacking superoxide dismutase is extended by overexpressing the anti apoptotic protein bcl 2 longo et al. 1999 .
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	the regulatory role of the bcl 2 members e.g. depends on their ability to regulate the mitochondrial function.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	in yeast bcl 2 proteins interact with the voltage dependent anion channel vdac and the adenine nucleotide translocator ant and these proteins are components of the mitochondrial permeability transition pore complex
16554	SLC25A6P1	solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6, pseudogene 1	adenine nucleotide translocator	1.0	in yeast bcl 2 proteins interact with the voltage dependent anion channel vdac and the adenine nucleotide translocator ant and these proteins are components of the mitochondrial permeability transition pore complex that is required for bax lethality marzo et al. 1998 ; shimizu et al. 1999 ; vander heiden et al. 1999
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	it has been suggested that the cytochrome c released into the cytosol as a consequence of pore opening has a pro apoptotic activity manon et al. 1997 ; minn et al. 1999 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	however ant is not essential for bax induced cytochrome c release from the mitochondria and contradictory results have been described regarding the role of vdac priault and priault ; shimizu et al. 2000 .
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	it should be noted that the importance of cytochrome c release in bax lethality was recently questioned as bax induces cell death in yeast cells expressing a functional cytochrome c_amp_#x2013;gfp fusion that is not relocalised into the cytosol roucou et
3951	FXN	frataxin	frataxin	1.0	this disorder results from a deficiency in frataxin a nuclear encoded mitochondrial protein with no homology to proteins of known function.
1260	C21orf2	chromosome 21 open reading frame 2	nuclear encoded mitochondrial protein	1.0	this disorder results from a deficiency in frataxin a nuclear encoded mitochondrial protein with no homology to proteins of known function.
3951	FXN	frataxin	frataxin	1.0	studies on the yeast frataxin homologue yfh1p suggest that this protein is an iron binding protein that plays a key role in regulation of iron homeostasis and resistance to oxidative stress.
3951	FXN	frataxin	frataxin	1.0	indeed yfh1p exhists as a monomer in the absence of iron but self aggregates in the presence of iron forming multimers able to sequester more than 16 iron atoms per frataxin molecule adamec et al. 2000 .
3951	FXN	frataxin	frataxin	1.0	both frataxin and yfh1p are processed in the mitochondria to a mature form that is essential for the control of mitochondrial iron homeostasis knight et al. 1998 ; branda et al. 1999 ; cavadini et al. 2000 .
3951	FXN	frataxin	frataxin	1.0	as the excess of iron is known to promote the formation of the highly reactive hydroxyl radicals the absence of an oxidative stress response may account for cellular dysfunction of frataxin deficient mutants.
9391	PRKAR2A	protein kinase, cAMP-dependent, regulatory, type II, alpha	protein kinase a	1.0	a under physiological conditions cells growing on glucose contain high levels of camp which activates protein kinase a pka and inhibits the general stress response mediated by msn2/4p and specific stress responses mediated by skn7p and yap1p.
12435	TXN	thioredoxin	thioredoxin	1.0	glutathione and thioredoxin antioxidant systems.
12435	TXN	thioredoxin	thioredoxin	1.0	a glutathione gsh and thioredoxin trx sh2 are oxidised during reduction of hydroperoxides and disulphide bonds.
12435	TXN	thioredoxin	thioredoxin	1.0	b nadph is essential for reduction of oxidised glutathione gssg and thioredoxin trx s 2 to gsh and trx sh 2 respectively.
4057	G6PD	glucose-6-phosphate dehydrogenase	glucose 6 phosphate dehydrogenase	1.0	zwf1 glucose 6 phosphate dehydrogenase gpd1 glycerol phosphate dehydrogenase gpp2 glycerol phosphate phosphatase ybr149w glycerol dehydrogenase dak1 dihydroxyacetone kinase gad1 glutamate decarboxylase uga5 succinate semialdehyde dehydrog
12435	TXN	thioredoxin	thioredoxin	1.0	a under non stress conditions thioredoxin reduces the cysteine residues and exposes the nes.