TOXI 12 |
| Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classic glycolytic enzyme, but its role as a mediator for cell death has recently been highlighted. Many groups reported that a pool of GAPDH translocates to the nucleus under a variety of stressors, most of which are associated with oxidative stress. Here I report its sequential molecular mechanism as follows: first, a catalytic cysteine in GAPDH (C150 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 Siah1, an E3 ubiquitin ligase, and stabilizes it; third, the GAPDH-Siah protein complex translocates to the nucleus, dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates in the nucleus, which results in cytotoxicity. I will further discuss a possible role of GAPDH in neurodegenerative disorders. |
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Protein Modification by Electrophiles
2:00 PM-4:10 PM, Sunday, 10 September 2006 Moscone Center -- Room 308, Oral
Division of Chemical Toxicology |