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

Makoto R. Hara, Nishant Agrawal, Sangwon Kim, Matthew B. Cascio, Masahiro Fujimuro, Yuji Ozeki, Masaaki Takahashi, Jaime H. Cheah, Stephanie K. Tankou, Lynda D Hester, Christopher D. Ferris, S. Diane Hayward, Solomon H Snyder, Akira Sawa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)665-674
Number of pages10
JournalNature Cell Biology
Volume7
Issue number7
DOIs
StatePublished - Jul 2005

Fingerprint

Glyceraldehyde-3-Phosphate Dehydrogenases
Cell Death
Nitric Oxide
Apoptosis
Nuclear Localization Signals
Ubiquitin-Protein Ligases
Macrophage Activation
Nuclear Proteins
Endotoxins
Glutamic Acid
Neurons

ASJC Scopus subject areas

  • Cell Biology

Cite this

S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. / Hara, Makoto R.; Agrawal, Nishant; Kim, Sangwon; Cascio, Matthew B.; Fujimuro, Masahiro; Ozeki, Yuji; Takahashi, Masaaki; Cheah, Jaime H.; Tankou, Stephanie K.; Hester, Lynda D; Ferris, Christopher D.; Hayward, S. Diane; Snyder, Solomon H; Sawa, Akira.

In: Nature Cell Biology, Vol. 7, No. 7, 07.2005, p. 665-674.

Research output: Contribution to journalArticle

Hara, MR, Agrawal, N, Kim, S, Cascio, MB, Fujimuro, M, Ozeki, Y, Takahashi, M, Cheah, JH, Tankou, SK, Hester, LD, Ferris, CD, Hayward, SD, Snyder, SH & Sawa, A 2005, 'S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding', Nature Cell Biology, vol. 7, no. 7, pp. 665-674. https://doi.org/10.1038/ncb1268
Hara, Makoto R. ; Agrawal, Nishant ; Kim, Sangwon ; Cascio, Matthew B. ; Fujimuro, Masahiro ; Ozeki, Yuji ; Takahashi, Masaaki ; Cheah, Jaime H. ; Tankou, Stephanie K. ; Hester, Lynda D ; Ferris, Christopher D. ; Hayward, S. Diane ; Snyder, Solomon H ; Sawa, Akira. / S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. In: Nature Cell Biology. 2005 ; Vol. 7, No. 7. pp. 665-674.
@article{e73f2be9336e410bb0bb40afe9b1ba07,
title = "S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding",
abstract = "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.",
author = "Hara, {Makoto R.} and Nishant Agrawal and Sangwon Kim and Cascio, {Matthew B.} and Masahiro Fujimuro and Yuji Ozeki and Masaaki Takahashi and Cheah, {Jaime H.} and Tankou, {Stephanie K.} and Hester, {Lynda D} and Ferris, {Christopher D.} and Hayward, {S. Diane} and Snyder, {Solomon H} and Akira Sawa",
year = "2005",
month = "7",
doi = "10.1038/ncb1268",
language = "English (US)",
volume = "7",
pages = "665--674",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding

AU - Hara, Makoto R.

AU - Agrawal, Nishant

AU - Kim, Sangwon

AU - Cascio, Matthew B.

AU - Fujimuro, Masahiro

AU - Ozeki, Yuji

AU - Takahashi, Masaaki

AU - Cheah, Jaime H.

AU - Tankou, Stephanie K.

AU - Hester, Lynda D

AU - Ferris, Christopher D.

AU - Hayward, S. Diane

AU - Snyder, Solomon H

AU - Sawa, Akira

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=22144477159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22144477159&partnerID=8YFLogxK

U2 - 10.1038/ncb1268

DO - 10.1038/ncb1268

M3 - Article

C2 - 15951807

AN - SCOPUS:22144477159

VL - 7

SP - 665

EP - 674

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 7

ER -