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Inhibitor of Apoptosis (IAP) and BIR-containing Proteins

  1. David L Vaux

Published Online: 15 SEP 2009

DOI: 10.1002/9780470015902.a0021570

eLS

eLS

How to Cite

Vaux, D. L. 2009. Inhibitor of Apoptosis (IAP) and BIR-containing Proteins. eLS. .

Author Information

  1. La Trobe University, Department of Biochemistry, Victoria 3086, Australia

Publication History

  1. Published Online: 15 SEP 2009

Abstract

The inhibitor of apoptosis (IAP) family of proteins are characterized by presence of one or more baculoviral IAP Repeat (BIR) domains, so they are also termed BIRCs, for ‘BIR-containing’ proteins. The first IAPs were identified in insect-attacking viruses, which use them to inhibit defensive apoptosis of the host cell. Subsequently, other BIR-containing proteins have been found in organisms from yeasts to mammals. The human IAP XIAP can block apoptosis by directly inhibiting caspases, whereas cIAP1 and cIAP2 inhibit apoptosis by reducing caspase-activating signals from tumour necrosis factor (TNF) receptor superfamily members. As the genes for some IAPs are amplified in cancers, they appear to be able to act as oncogenes. IAP-antagonist compounds modelled on the IAP antagonist Smac/Diablo are being developed for the treatment of cancer, and are currently undergoing clinical trials.

Key concepts

  • All IAPs bear at least one BIR domain, but not all BIR-containing proteins are inhibitors of apoptosis.

  • XIAP can block apoptosis by directly inhibiting caspases, but cIAP1 and cIAP2 inhibit apoptosis by reducing caspase-activating signals from TNF receptor superfamily members, and by promoting activation of canonical NFκB pathways rather than noncanonical NFκB pathways.

  • Genes for some IAPs are amplified in cancers, and IAP-antagonist compounds modelled on the IAP antagonist Smac/Diablo are being developed for the treatment of cancer.

  • Survivin and BRUCE are not apoptosis inhibitors, but are needed for cell division.

Keywords:

  • XIAP;
  • cIAP1;
  • cIAP2;
  • IAP;
  • Survivin;
  • BIR