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

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.

Pubmed ID: 10411906


  • Zhang L
  • Chen J
  • Fu H


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

July 20, 1999

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM53165

Mesh Terms

  • 14-3-3 Proteins
  • Animals
  • Apoptosis
  • Cell Line
  • DNA Fragmentation
  • 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
  • Proteins
  • Signal Transduction
  • Transfection
  • Tyrosine 3-Monooxygenase