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X-linked IAP is a direct inhibitor of cell-death proteases

Q L Deveraux1, R Takahashi, G S Salvesen

  • 1The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037, USA.

Nature
|July 17, 1997
PubMed

Insights

Inhibitor-of-apoptosis (IAP) proteins suppress programmed cell death. This study reveals that X-linked IAP directly inhibits caspase-3 and caspase-7, key cell death proteases, clarifying IAP

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The inhibitor-of-apoptosis (IAP) gene family plays a crucial role in regulating programmed cell death across diverse animal species.
  • While ectopic expression of IAP proteins is known to prevent cell death, the underlying mechanism remains largely unelucidated.

Purpose of the Study:

  • To elucidate the mechanism by which IAP proteins inhibit apoptosis.
  • To identify the specific caspase targets of human X-chromosome-linked IAP (XIAP).

Main Methods:

  • Investigated the interaction between human XIAP and caspases.
  • Assessed the inhibitory effect of XIAP on caspase-3 and caspase-7 activity in vitro.

Main Results:

  • Demonstrated that human XIAP directly inhibits the activity of caspase-3 and caspase-7.
  • Identified caspase-3 and caspase-7 as direct targets of XIAP-mediated inhibition.

Conclusions:

  • The findings propose a direct inhibitory mechanism for IAPs in regulating apoptosis.
  • XIAP's inhibition of caspases provides a molecular explanation for its cell death-suppressing function in mammals.

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