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The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum

David G Breckenridge1, Mai Nguyen, Stephan Kuppig

  • 1Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, QC, Canada H3G 1Y6.

Proceedings of the National Academy of Sciences of the United States of America
|March 28, 2002
PubMed

Insights

Researchers discovered a new caspase-8 isoform, procaspase-8L, that interacts with the BAP31 complex. This interaction at the endoplasmic reticulum regulates apoptosis and cell death signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Signaling

Background:

  • BAP31 is an endoplasmic reticulum membrane protein and caspase-8 substrate.
  • Caspase-8 plays a critical role in initiating apoptosis.
  • Understanding caspase regulation is key to controlling cell death.

Purpose of the Study:

  • To identify and characterize a novel isoform of procaspase-8.
  • To elucidate the role of BAP31 in the regulation of procaspase-8.
  • To investigate a new pathway for caspase-8 activation in apoptosis.

Main Methods:

  • Procaspase-8L isoform identification and characterization.
  • Analysis of procaspase-8L interaction with the BAP31 complex.
  • Gene deletion studies to assess the function of BAP31 and BAP29.
  • Assessment of downstream caspase activation and cell death.

Main Results:

  • Procaspase-8L, characterized by its N-terminal extension (Nex) domain, is selectively recruited to the BAP31 complex.
  • BAP31 and BAP29 are essential for procaspase-8L processing via a FADD-independent, BCL-2-sensitive mechanism.
  • Deletion of Bap29/31 or a dominant-negative Nex mutant inhibits downstream caspase activation and E1A-induced cell death.

Conclusions:

  • The BAP31 complex at the endoplasmic reticulum provides a platform for procaspase-8L recruitment and activation.
  • This identifies a novel endoplasmic reticulum-initiated pathway for regulating initiator caspase-8 during apoptosis.
  • The Nex domain of procaspase-8L is crucial for its selective interaction with BAP31 and subsequent apoptotic signaling.

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