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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type II cells

M Hasegawa1, K Kawase, N Inohara

  • 1Center for the Development of Molecular Target Drugs, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.

Oncogene
|September 12, 2006
PubMed

Insights

Apoptosis-associated speck-like protein containing a CARD (ASC) mediates cell death signals. This study reveals ASC triggers apoptosis via caspase-8, with caspase-9 involvement varying by cell type.

Area of Science:

  • Cellular Biology
  • Molecular Mechanisms of Apoptosis

Background:

  • Apoptosis-associated speck-like protein containing a CARD (ASC) is crucial for apoptosis and inflammation.
  • The precise mechanisms of ASC-mediated apoptosis remain incompletely understood.
  • ASC's role in tumor suppression highlights the need to elucidate its apoptotic pathways.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying ASC-mediated apoptosis.
  • To identify key caspases and regulatory proteins involved in ASC signaling.
  • To determine if ASC-mediated apoptosis follows distinct pathways similar to death receptors.

Main Methods:

  • Utilized a CARD12-Nod2 chimeric protein to induce ASC-mediated apoptosis.
  • Employed dominant-negative mutants, small-interfering RNAs, and peptide inhibitors for caspases.
  • Assessed apoptosis sensitivity in various cell lines, including Bax-deficient and Clarp-/- cells.

Main Results:

  • Caspase-8 was essential for ASC-mediated apoptosis across most cell types.
  • Caspase-9 requirement for ASC-mediated apoptosis was cell-type dependent.
  • Caspase-8 inhibitor CLARP suppressed ASC-induced apoptosis, while its absence enhanced sensitivity.
  • ASC-mediated apoptosis was inhibited by Bcl-2/Bcl-XL in type-II cells but not type-I cells.
  • Bid cleavage occurred upon ASC activation, and Bid suppression reduced ASC-mediated apoptosis in type-II cells.

Conclusions:

  • ASC mediates apoptosis through caspase-8, similar to death receptor pathways.
  • ASC-induced apoptosis exhibits type-I and type-II characteristics depending on the cell context.
  • These findings clarify the complex role of ASC in apoptosis regulation.

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