Identification of XAF1 as an antagonist of XIAP anti-Caspase activity

Nat Cell Biol. 2001 Feb;3(2):128-33. doi: 10.1038/35055027.

Abstract

The inhibitors of apoptosis (IAPs) suppress apoptosis through the inhibition of the caspase cascade and thus are key proteins in the control of cell death. Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family. XIAP suppresses caspase activation and cell death in vitro, and XAF1 antagonizes these XIAP activities. Expression of XAF1 triggers a redistribution of XIAP from the cytosol to the nucleus. XAF1 is ubiquitously expressed in normal tissues, but is present at low or undetectable levels in many different cancer cell lines. Loss of control over apoptotic signalling is now recognized as a critical event in the development of cancer. Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Blotting, Northern
  • Blotting, Western
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Survival
  • Culture Media, Serum-Free
  • Enzyme Inhibitors / metabolism*
  • Etoposide / pharmacology
  • Genes, Reporter
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Plasmids / genetics
  • Plasmids / metabolism
  • Proteins / antagonists & inhibitors*
  • Proteins / genetics
  • Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques
  • X-Linked Inhibitor of Apoptosis Protein
  • Zinc Fingers

Substances

  • Antineoplastic Agents, Phytogenic
  • Caspase Inhibitors
  • Culture Media, Serum-Free
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • X-Linked Inhibitor of Apoptosis Protein
  • XAF1 protein, human
  • XIAP protein, human
  • Etoposide
  • Caspases

Associated data

  • GENBANK/X99699