RGD Reference Report - S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. - Rat Genome Database

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S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding.

Authors: Hara, MR  Agrawal, N  Kim, SF  Cascio, MB  Fujimuro, M  Ozeki, Y  Takahashi, M  Cheah, JH  Tankou, SK  Hester, LD  Ferris, CD  Hayward, SD  Snyder, SH  Sawa, A 
Citation: Hara MR, etal., Nat Cell Biol. 2005 Jul;7(7):665-74. Epub 2005 Jun 12.
RGD ID: 8554488
Pubmed: PMID:15951807   (View Abstract at PubMed)
DOI: DOI:10.1038/ncb1268   (Journal Full-text)

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) influences cytotoxicity, translocating to the nucleus during apoptosis. 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 Siah1 (an E3 ubiquitin ligase), nuclear translocation and apoptosis. S-nitrosylation of GAPDH augments its binding to Siah1, whose nuclear localization signal mediates translocation of GAPDH. GAPDH stabilizes Siah1, facilitating its degradation of nuclear proteins. Activation of macrophages by endotoxin and of neurons by glutamate elicits GAPDH-Siah1 binding, nuclear translocation and apoptosis, which are prevented by NO deletion. The NO-S-nitrosylation-GAPDH-Siah1 cascade may represent an important molecular mechanism of cytotoxicity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuron apoptotic process involved_inIMP 8554488; 8554488; 8554488PMID:15951807UniProt 
protein stabilization involved_inIDA 8554488; 8554488PMID:15951807UniProt 
ubiquitin-dependent protein catabolic process involved_inIDA 8554488PMID:15951807UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytosol located_inIDA 8554488; 8554488; 8554488PMID:15951807UniProt 
nucleus located_inIDA 8554488; 8554488; 8554488PMID:15951807UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Gapdh  (glyceraldehyde-3-phosphate dehydrogenase)
LOC134486952  (glyceraldehyde-3-phosphate dehydrogenase)
Siah1  (siah E3 ubiquitin protein ligase 1)


Additional Information