HUGO ID Detailed Result 3711


HUGO ID 3711
Symbol FKBP1A
Name FK506 binding protein 1A, 12kDa
#Occurrence 43
#Paper 1

 


PMID Match String Actual String Score Flanking text Edited by Edit
10077670rotamaserotamase1.0because both groups of drugs inhibit the rotamase activity of cyclophilins cyp but only the immunosuppressant analogs inhibit calcineurin activity these data suggest that rotamase inhibition underlies the enhanced cell death after sodv148g expression.  
10077670rotamaserotamase1.0the importance of rotamase activity in mutant sod mediated apoptosis was supported by experiments showing that overexpressed wild type cyclophilin a cypa but not cypa with a rotamase active site point mutation protected cells from death after sodv148g expression.  
10077670rotamaserotamase1.0these data suggest that mutant sod produces a greater need for rotamase and also highlights possible new therapeutic strategies in fals.  
10077670rotamaserotamase1.0rotamase activity assay.  
10077670rotamaserotamase1.0a previously published 21 chymotrypsin coupled assay was used to measure rotamase activity.  
10077670rotamaserotamase1.0cells were treated with csa and were harvested as described above for the rotamase assay.  
10077670rotamaserotamase1.0fig. 3 a shows that csa csg and fk506 immunosuppressant drugs known to inhibit calcineurin and the rotamase activity of immunophilin potentiated cell death induced by sodv148g expression fig 3 a .  
10077670rotamaserotamase1.0we also examined the effect of pkf 211_amp_#x02013;811 and psc 833 nonimmunosuppressant csa analogs that inhibit cyclophilin rotamase activity but not calcineurin 22 23 .  
10077670rotamaserotamase1.0the results suggest that csa enhances sodv148g induced cell death by inhibiting cyclophilin rotamase activity and not because of calcineurin inhibition.  
10077670rotamaserotamase1.0effect of csa on rotamase activity levels.  
10077670rotamaserotamase1.0the above studies suggested that csa and its immunosuppressive analogs might enhance sod mutant induced cell death through its interference with rotamase activity.  
10077670rotamaserotamase1.0it also raised the question as to whether there is a preexisting difference in the level of rotamase activity between sodv148g expressing and mock cells making the former cells more sensitive to csa.  
10077670rotamaserotamase1.0therefore we measured rotamase activity in mock wt and mutant sod expressing cells before and after csa treatment.  
10077670rotamaserotamase1.0the data show that all cells had a similar amount of rotamase activity before csa treatment and that csa decreased rotamase activity to a similar level in all three groups table 1 with no significant differences in this inhibition in the sodv148g expressing cells vs. other csa treated groups.  
10077670rotamaserotamase1.0these results suggested that mutant sod expressing cells might be more sensitive to effects of decreased rotamase activity.  
10077670rotamaserotamase1.0our interpretation of these studies is that human sod/rodent sod heterodimers that are formed in the transiently expressing cells may be more sensitive to conformational changes resulting from rotamase inhibition than the homogeneous rodent homodimers present in controls.  
10077670rotamaserotamase1.0to further examine the role of cyclophilin rotamase activity on mutant sod induced cell death we transfected ngf differentiated pc12 cells with wild type cypa cypawt cdna or cypa r55a cdna that contains a point mutation in the putative rotamase active 
10077670rotamaserotamase1.0 activity on mutant sod induced cell death we transfected ngf differentiated pc12 cells with wild type cypa cypawt cdna or cypa r55a cdna that contains a point mutation in the putative rotamase active site.  
10077670rotamaserotamase1.0these results suggest that the rotamase function of cypa protects cells from death induced by sodv148g.  
10077670rotamaserotamase1.0these results suggest that modulating the rotamase activity is vital for the survival of mutant sod expressing cells.  
10077670rotamaserotamase1.0in addition to inhibiting calcineurin and blocking the mptp csa blocks peptidyl prolyl isomerase rotamase activity of cyclophilins.  
10077670rotamaserotamase1.0immunophilin rotamase activity is believed to have a variety of actions in neurons 15 .  
10077670rotamaserotamase1.0to test whether csa enhanced sodv148g toxicity through rotamase inhibition we examined the effect of immunosuppressants csa csg and fk506 as well as nonimmunosuppressants pkf 211_amp_#x02013;811 or psc 833 .  
10077670rotamaserotamase1.0nonimmunosuppressants do not influence calcineurin activity but do inhibit rotamase activity.  
10077670rotamaserotamase1.0we found that both drug classes enhanced apoptosis induced by mutant sod indicating that the action of csa may be related to rotamase inhibition and not to calcineurin inhibition.  
10077670rotamaserotamase1.0a role for rotamase in mutant sod toxicity was supported by experiments comparing mutant sod induced cell death after expression of cypawt vs. an isomerase activity deficient mutant cypa r55a .  
10077670rotamaserotamase1.0although a recent report concluded that cypa r55a may have more rotamase activity than previously suspected 33 34 it appears that this residual activity is insufficient to permit folding of fully functional proteins 17 .  
10077670rotamaserotamase1.0our data highlight the importance of rotamase activity in modifying the effect of mutant sod.  
10077670rotamaserotamase1.0the findings that rotamase activity protects cells from mutant sod induced cell death and that there is roughly similar rotamase activity after csa treatment in wt and mutant sod expressing cells suggests that cells expressing mutant sod have a greater reliance on rotamase activity and has implications on our understanding of  
10077670rotamaserotamase1.0 activity after csa treatment in wt and mutant sod expressing cells suggests that cells expressing mutant sod have a greater reliance on rotamase activity and has implications on our understanding of the mechanism of this toxicity.  
10077670rotamaserotamase1.0the increased protein turnover may enhance the need for rotamase function.  
10077670rotamaserotamase1.0rotamase also may be needed to refold proteins that are partly denatured by oxidative damage.  
10077670rotamaserotamase1.0rotamase may be required to maintain proteins in a correct conformation during their transport in motor axons.  
10077670rotamaserotamase1.0rotamase also may have a role in the normal folding of sod itself to help stabilize the enzyme or its dimers.  
10077670rotamaserotamase1.0 mutant sod expression than after sodwt expression suggesting that the mutant enzyme was more sensitive than wt to the effects of csa perhaps because the mutant sod was more sensitive to a decline in rotamase activity and the consequences of misfolding.  
10077670rotamaserotamase1.0it also may be that other proteins perhaps ones that interact with sod are more sensitive to decreased rotamase activity.  
10077670rotamaserotamase1.0our observations have implications regarding possible therapy of fals suggesting the potential use of chaperone proteins or of agents that modulate rotamase activity to correct the deficits.  
10077670rotamaserotamase1.0rather our studies suggest that these drugs worsen the fals mediated cell death because of rotamase inhibition.  
10077670rotamaserotamase1.0table 1 mean rotamase and sod activity _amp_#x0005b;percent of control mock infected pc12 cells_amp_#x0005d;  
10077670rotamaserotamase1.0suppressants bind immunophilins _amp_#x0005b;the drug receptor: e.g. cyclophilins cyp or fk binding protein_amp_#x0005d; and the drug immunophilin complex inhibits calcineurin activity as well as the rotamase peptidyl prolyl cis_amp_#x02013;trans isomerase activity of the immunophilins 13 14 .  
10077670rotamaserotamase1.0rotamase facilitates cis_amp_#x02013;trans isomerization of the peptide bond on the n terminal side of proline residues aids normal folding and assembly of proteins including sod and has other cellular functi 
10077670rotamaserotamase1.0most importantly we show that immunosuppressant drugs csa csg and fk506 enhance cell death induced by mutant sod and that this enhancement depends on rotamase inhibition.  
10077670rotamaserotamase1.0these findings suggest that mutant sod may lead to increased protein damage or turnover and a greater reliance on rotamase activity.