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Apoptosis inhibitor 5 is an endogenous inhibitor of caspase-2

Gergely Imre1, Jean Berthelet1, Jan Heering2

  • 1MSU-FZI, Institute of Immunology, University Medical Center Mainz, JGU, Mainz, Germany.

EMBO Reports
|March 25, 2017
PubMed

Insights

Apoptosis inhibitor 5 (API5) directly inhibits caspase-2, a key enzyme in cell death. API5 blocks caspase-2 dimerization and activation, revealing a new regulatory mechanism for this important protease.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Caspases are crucial enzymes mediating apoptosis.
  • Caspase-2, the most conserved caspase, regulates cell death, autophagy, genomic stability, and aging.
  • Caspase-2 activation requires dimerization, typically via high molecular weight protein complexes.

Purpose of the Study:

  • To identify endogenous inhibitors of caspase-2.
  • To elucidate the mechanism by which API5/AAC11 regulates caspase-2 activity.
  • To understand the role of API5 in caspase-2-mediated apoptosis.

Main Methods:

  • Protein-protein interaction assays to demonstrate API5 binding to caspase-2.
  • In vitro assays using recombinant proteins to assess inhibition.
  • Cellular studies involving API5 depletion to evaluate caspase-2 activation and apoptosis.

Main Results:

  • Apoptosis inhibitor 5 (API5/AAC11) directly binds to the caspase recruitment domain (CARD) of caspase-2.
  • API5 inhibits caspase-2 dimerization and activation, particularly of full-length caspase-2.
  • Depletion of API5 increases caspase-2 dimerization and activation, sensitizing cells to apoptosis.

Conclusions:

  • API5/AAC11 is a direct endogenous inhibitor of caspase-2.
  • API5 regulates caspase-2 activation by preventing its dimerization.
  • This finding provides new insights into the regulation of caspase-2, a poorly understood caspase.
Keywords:
apoptosisapoptosis inhibitor 5caspase‐2cell deathpore‐forming toxins

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