Nitric oxide-GAPDH-Siah: a novel cell death cascade.

Nitric oxide-GAPDH-Siah: a novel cell death cascade. Research Abstract Details 

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Nitric oxide-GAPDH-Siah: a novel cell death cascade. Abstract Text:

Makoto R Hara,Solomon H Snyder,

1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extremely abundant glycolytic enzyme, and exemplifies the class of proteins with multiple, seemingly unrelated functions. Recent studies indicate that it is a major intracellular messenger mediating apoptotic cell death. This paper reviews the GAPDH cell death cascade and discusses its clinical relevance. 2. A wide range of apoptotic stimuli activate NO formation, which S-nitrosylates GAPDH. The S-nitrosylation abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah, an E3-ubiquitin-ligase, which translocates GAPDH to the nucleus. In the nucleus, GAPDH stabilizes the rapidly turning over Siah, enabling it to degrade selected target proteins and affect apoptosis. 3. The cytotoxicity of mutant Huntingtin (mHtt) requires nuclear translocation which appears to be mediated via a ternary complex of GAPDH-Siah-mHtt. The neuroprotective actions of the monoamine oxidase inhibitor R-(-)-deprenyl (deprenyl) reflect blockade of GAPDH-Siah binding. Thus, novel cytoprotective therapies may emerge from agents that prevent GAPDH-Siah binding.

Nitric oxide-GAPDH-Siah: a novel cell death cascade. Publishing Authors By Initials

MR Hara,SH Snyder,

For similar enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research abstracts see: enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research

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MEDLINE DATE:

Nitric oxide-GAPDH-Siah: a novel cell death cascade. Journal Published:

PUBLICATION TYPE: Review

Journal: Cellular and molecular neurobiology

VOLUME: 26

Page Numbers: 527-38

Journal Abbreviation: Cell. Mol. Neurobiol.

ISSN: 0272-4340

DAY: 22

MONTH: 04

YEAR: 2006

Nitric oxide-GAPDH-Siah: a novel cell death cascade. Information

Number of References: 54

LANGUAGE: eng

NlmUniqueID: 8200709

Nitric oxide-GAPDH-Siah: a novel cell death cascade. Keywords Mesh Terms:

KEYWORDS: Ubiquitin-Protein Ligases

MESH TERMS: physiology

Chemical & Substance for Abstract: Nitric oxide-GAPDH-Siah: a novel cell death cascade. Information

Substance Name: seven in absentia proteins

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Nitric oxide-GAPDH-Siah: a novel cell death cascade.

AFFILIATION: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Country: United States

AGENCY: United States NIDA

GRANT: DA00074

ACRONYM: DA

MEDLINETA: Cell Mol Neurobiol

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