| Interacting proteins: Q8IUQ4 and P04406 |
Pubmed |
SVM Score :0.0 |
| S nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah 1 binding . ^^^ Here we report a signalling pathway in which nitric oxide ( NO ) generation that follows apoptotic stimulation elicits S nitrosylation of GAPDH , which triggers binding to Siah 1 ( an E 3 ubiquitin ligase ) , nuclear translocation and apoptosis . ^^^ S nitrosylation of GAPDH augments its binding to Siah 1 , whose nuclear localization signal mediates translocation of GAPDH . ^^^ GAPDH stabilizes Siah 1 , facilitating its degradation of nuclear proteins . ^^^ Activation of macrophages by endotoxin and of neurons by glutamate elicits GAPDH Siah 1 binding , nuclear translocation and apoptosis , which are prevented by NO deletion . ^^^ |
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| Interacting proteins: Q8IUQ4 and P04406 |
Pubmed |
SVM Score :0.0 |
| Cytotoxic stimuli , via nitric oxide generation , lead to the binding of GAPDH to the protein Siah 1 , translocation of GAPDH Siah 1 to the nucleus , and ultimately cell death . ^^^ |
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| Interacting proteins: Q8IUQ4 and P04406 |
Pubmed |
SVM Score :0.0 |
| We establish that the nuclear translocation and associated cytotoxicity of mHtt reflect a ternary complex of mHtt with GAPDH and Siah 1 , a ubiquitin E 3 ligase . ^^^ Overexpression of GAPDH or Siah 1 enhances nuclear translocation of mHtt and cytotoxicity , whereas GAPDH mutants that can not bind Siah 1 prevent translocation . ^^^ Depletion of GAPDH or Siah 1 by RNA interference diminishes nuclear translocation of mHtt . . ^^^ |
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| Interacting proteins: Q8IUQ4 and P04406 |
Pubmed |
SVM Score :0.0 |
| In mice treated with the dopamine neuronal toxin 1 methyl 4 phenyl 1 , 2 , 3 , 6 tetrahydropyridine ( MPTP ) , low doses of deprenyl prevent binding of GAPDH and Siah 1 in the dopamine enriched corpus striatum . . ^^^ |
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| Interacting proteins: Q8IUQ4 and P04406 |
Pubmed |
SVM Score :0.0 |
| The structure is also used to build a qualitative model of the complex between GAPDH and the E 3 ubiquitin ligase Siah 1 . ^^^ The model suggests that the convex surface near GAPDH Lys 227 interacts with a large shallow groove of the Siah 1 dimer . ^^^ These results are discussed in the context of the recently discovered NO S nitrosylation GAPDH Siah 1 apoptosis cascade . . ^^^ |
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| Interacting proteins: Q8IUQ4 and P04406 |
Pubmed |
SVM Score :0.0 |
| At the molecular level , sequential steps lead to nuclear translocation of GAPDH during cell death as follows : first , a catalytic cysteine in GAPDH ( C 150 in rat GAPDH ) is S nitrosylated by nitric oxide ( NO ) that is generated from inducible nitric oxide synthase ( iNOS ) and / or neuronal NOS ( nNOS ) ; second , the modified GAPDH becomes capable of binding with Siah 1 , an E 3 ubiquitin ligase , and stabilizes it ; third , the GAPDH Siah protein complex translocates to the nucleus , dependent on Siah 1 ' s nuclear localization signal , and degrades Siah 1 ' s substrates in the nucleus , which results in cytotoxicity . ^^^ |
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