PMID- 10411906 OWN - NLM STAT- MEDLINE DCOM- 19990823 LR - 20190501 IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 96 IP - 15 DP - 1999 Jul 20 TI - Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. PG - 8511-5 AB - 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. FAU - Zhang, L AU - Zhang L AD - Department of Pharmacology, Cell, and Developmental Biology, Emory University, Atlanta, GA 30322, USA. FAU - Chen, J AU - Chen J FAU - Fu, H AU - Fu H LA - eng GR - R01 GM053165/GM/NIGMS NIH HHS/United States GR - R29 GM053165/GM/NIGMS NIH HHS/United States GR - GM53165/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (14-3-3 Proteins) RN - 0 (Luminescent Proteins) RN - 0 (Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - EC 2.7.11.25 (MAP3K5 protein, human) SB - IM MH - 14-3-3 Proteins MH - Animals MH - Apoptosis/*genetics MH - Cell Line MH - DNA Fragmentation/genetics MH - Gene Expression Regulation MH - Green Fluorescent Proteins MH - Humans MH - Luminescent Proteins MH - MAP Kinase Kinase Kinase 5 MH - *MAP Kinase Kinase Kinases MH - Mutation MH - Phosphorylation MH - Protein Binding MH - Protein-Serine-Threonine Kinases/*genetics/metabolism MH - Proteins/*metabolism MH - Signal Transduction MH - Transfection MH - *Tyrosine 3-Monooxygenase PMC - PMC17547 EDAT- 1999/07/21 00:00 MHDA- 1999/07/21 00:01 CRDT- 1999/07/21 00:00 PHST- 1999/07/21 00:00 [pubmed] PHST- 1999/07/21 00:01 [medline] PHST- 1999/07/21 00:00 [entrez] AID - 10.1073/pnas.96.15.8511 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8511-5. doi: 10.1073/pnas.96.15.8511.