An IAP-IAP complex inhibits apoptosis

J Biol Chem. 2004 Aug 13;279(33):34087-90. doi: 10.1074/jbc.C400236200. Epub 2004 Jun 24.

Abstract

Regulators of apoptosis are thought to work in concert, but the molecular interactions of this process are not understood. Here, we show that in response to cell death stimulation, survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats. Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP(-/-) cells. Therefore, orchestration of an IAP-IAP complex regulates apoptosis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Baculoviridae / metabolism
  • Caspase 9
  • Caspases / metabolism
  • Cell Death
  • Cell Line
  • Cell Line, Tumor
  • Cysteine Endopeptidases / metabolism
  • Dose-Response Relationship, Drug
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Glutathione Transferase / metabolism
  • Humans
  • Immunoblotting
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Multienzyme Complexes / metabolism
  • Neoplasm Proteins
  • Precipitin Tests
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Proteins / chemistry
  • Proteins / physiology*
  • Recombinant Proteins / metabolism
  • Survivin
  • Time Factors
  • Transfection
  • Transgenes
  • Ubiquitin / metabolism
  • X-Linked Inhibitor of Apoptosis Protein

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Multienzyme Complexes
  • Neoplasm Proteins
  • Proteins
  • Recombinant Proteins
  • Survivin
  • Ubiquitin
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Glutathione Transferase
  • CASP9 protein, human
  • Casp9 protein, mouse
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex