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Caspase 10 levels are increased following DNA damage in a p53-dependent manner

Bart Rikhof1, Paul G Corn, Wafik S El-Deiry

  • 1Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Departments of Medicine, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Cancer Biology & Therapy
|December 23, 2003
PubMed

Insights

The tumor suppressor p53 activates caspase 10 (an initiator caspase) in response to DNA damage, promoting apoptosis. This study identifies caspase 10 as a direct transcriptional target of p53.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The p53 protein is a critical regulator of cellular stress responses, including DNA damage.
  • p53 influences cell-cycle arrest, DNA repair, and apoptosis, but the precise mechanisms determining these outcomes are not fully understood.
  • Initiator caspases like caspase 8 and caspase 10 play key roles in initiating apoptosis.

Purpose of the Study:

  • To investigate the role of p53 in the regulation of initiator caspases, specifically caspase 10, following DNA damage.
  • To determine if caspase 10 is a direct transcriptional target of p53.

Main Methods:

  • Treatment of cells with DNA damaging agents (etoposide, adriamycin).
  • Quantitative analysis of caspase 10 and caspase 8 mRNA and protein levels.
  • Chromatin immunoprecipitation (ChIP) assays to assess p53 binding to the caspase 10 gene locus.

Main Results:

  • DNA damaging agents induced both mRNA and protein levels of caspase 10 in a p53-dependent manner.
  • Caspase 8 levels remained unaffected by DNA damage.
  • ChIP assays demonstrated direct in vivo binding of p53 to the caspase 10 gene, confirming it as a transcriptional target.

Conclusions:

  • Caspase 10 is a direct transcriptional target of p53 and is upregulated in response to DNA damage.
  • The induction of caspase 10 by p53 may be a key factor mediating p53-dependent apoptosis.
  • This finding sheds light on the molecular mechanisms by which p53 controls cell fate decisions after DNA damage.

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