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Identification of a conserved anti-apoptotic protein that modulates the mitochondrial apoptosis pathway

Yu Zhang1, Elisabet Johansson, Marian L Miller

  • 1School of Pharmacy, University of Cincinnati, Cincinnati, Ohio, United States of America.

Plos One
|October 8, 2011
PubMed

Insights

Researchers discovered a conserved protein, C9orf82 (Conserved Anti-Apoptotic Protein - CAAP), that inhibits apoptosis. Its knockdown triggers cell death, suggesting CAAP as a potential target for cancer therapy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis is a crucial cellular process regulated by caspases.
  • The role of conserved proteins in apoptosis regulation is not fully understood.

Purpose of the Study:

  • To identify and characterize a novel protein involved in apoptosis regulation.
  • To elucidate the mechanism by which C9orf82 influences apoptosis.
  • To evaluate the potential of C9orf82 as a therapeutic target.

Main Methods:

  • RNA interference (RNAi) for gene knockdown.
  • Apoptosis assays in lung and breast carcinoma cell lines.
  • Western blotting to detect protein expression and activation.
  • Caspase activity assays.

Main Results:

  • C9orf82, structurally similar to death effector domains, was identified as Conserved Anti-Apoptotic Protein (CAAP).
  • RNAi-mediated knockdown of CAAP induced apoptosis in cancer cells, dependent on caspase-3 and caspase-10.
  • CAAP knockdown led to caspase-10 activation, tBid generation, and caspase-9 activation, indicating a caspase-10 dependent mitochondrial feedback loop.
  • CAAP knockdown sensitized cells to chemotherapy-induced apoptosis.

Conclusions:

  • CAAP functions as an anti-apoptotic protein regulating a caspase-10 dependent mitochondrial amplification loop.
  • CAAP is a potential therapeutic target for enhancing chemotherapy efficacy in cancer treatment.

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