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Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1

B N Chau1, E H Cheng, D A Kerr

  • 1Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Schools of Medicine and Public Health, Baltimore, Maryland 21205, USA.

Molecular Cell
|August 19, 2000
PubMed

Insights

A novel apoptosis inhibitor, Aven, binds to Bcl-x(L) and Apaf-1, suggesting it regulates cell death at a late stage. Aven impairs Apaf-1-mediated caspase activation, representing a new class of cell death regulator.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Bcl-x(L) is an antiapoptotic protein involved in regulating cell death.
  • Its function at various stages of the cell death pathway is under investigation.
  • The precise mechanisms by which Bcl-x(L) exerts its antiapoptotic effects, particularly at later stages, remain to be fully elucidated.

Purpose of the Study:

  • To identify novel regulators of apoptosis.
  • To investigate the role of Bcl-x(L) in late-stage cell death.
  • To characterize a newly discovered apoptosis inhibitor, Aven.

Main Methods:

  • Yeast two-hybrid screening to identify binding partners.
  • Biochemical assays to assess protein interactions and enzyme activity.
  • Cell-free extracts and apoptosis induction systems to evaluate inhibitor function.

Main Results:

  • A novel apoptosis inhibitor, Aven, was identified.
  • Aven binds to Bcl-x(L) and the caspase regulator Apaf-1.
  • Aven inhibits Apaf-1 self-association and caspase activation, suppressing apoptosis.
  • Aven's interaction with Bcl-x(L) requires Bcl-x(L)'s antiapoptotic activity.

Conclusions:

  • Aven represents a new class of cell death regulator.
  • Aven functions at a post-mitochondrial, late step in the apoptosis pathway.
  • Aven's mechanism involves interfering with Apaf-1-mediated caspase activation.

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