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PMID: 10411906 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 15 ·1999-07-20 ·Pages 8511-5

Zhang L, Chen J, Fu H

Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component of a signaling pathway induced by many death stimuli, including tumor necrosis factor alpha, Fas, and the anticancer drugs cisplatin and paclitaxel. Here we report that ASK1 proapoptotic activity is antagonized by association with 14-3-3 proteins. We found that ASK1 specifically bound 14-3-3 proteins via a site involving Ser-967 of ASK1. Interestingly, overexpression of 14-3-3 in HeLa cells blocked ASK1-induced apoptosis whereas disruption of the ASK1/14-3-3 interaction dramatically accelerated ASK1-induced cell death. Targeting of ASK1 by a 14-3-3-mediated survival pathway may provide a novel mechanism for the suppression of apoptosis.

MeSH Terms
14-3-3 Proteins Animals Apoptosis/genetics Cell Line DNA Fragmentation/genetics Gene Expression Regulation Green Fluorescent Proteins Humans Luminescent Proteins MAP Kinase Kinase Kinase 5 MAP Kinase Kinase Kinases Mutation Phosphorylation Protein Binding Protein Serine-Threonine Kinases/genetics,metabolism Proteins/metabolism Signal Transduction Transfection Tyrosine 3-Monooxygenase
Chemicals
14-3-3 Proteins Luminescent Proteins Proteins Green Fluorescent Proteins Tyrosine 3-Monooxygenase Protein Serine-Threonine Kinases MAP Kinase Kinase Kinase 5 MAP Kinase Kinase Kinases MAP3K5 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhang L
Department of Pharmacology, Cell, and Developmental Biology, Emory University, Atlanta, GA 30322, USA.
Chen J
Fu H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.15.8511
Published
1999-07-20
Pages
8511-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17547
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053165 · United States
NIGMS NIH HHS · R29 GM053165 · United States
NIGMS NIH HHS · GM53165 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.15.8511 PMC Full Text View journal details
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