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Transcription factor Sox4 is required for PUMA-mediated apoptosis induced by histone deacetylase inhibitor, TSA

Sang-Min Jang1, Eun-Jin Kang, Jung-Woong Kim

  • 1Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.

Biochemical and Biophysical Research Communications
|August 7, 2013
PubMed

Insights

The transcription factor Sox4 induces PUMA expression, a key regulator of cell death, in a p53-independent manner. This finding is crucial for understanding apoptosis in cancer cells treated with trichostatin A (TSA).

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Mechanisms

Background:

  • PUMA (p53 upregulated modulator of apoptosis) regulates both p53-dependent and p53-independent cell death.
  • PUMA induction by DNA damage typically relies on p53.
  • Factors driving p53-independent PUMA induction remain largely uncharacterized.

Purpose of the Study:

  • To identify transcription factors involved in p53-independent PUMA induction.
  • To investigate the role of Sox4 in PUMA expression and apoptosis.
  • To elucidate the mechanism of Sox4-mediated PUMA regulation in response to TSA.

Main Methods:

  • Utilized p53-null human lung cancer cell line (H1299).
  • Assessed PUMA mRNA and protein levels following Sox4 ectopic expression and knockdown.
  • Employed luciferase assays and chromatin immunoprecipitation to study Sox4-PUMA promoter interaction.

Main Results:

  • Sox4 overexpression increased PUMA mRNA and protein levels.
  • TSA-induced PUMA up-regulation was dependent on Sox4.
  • Sox4 recruits p300 to the PUMA promoter, enhancing gene expression in response to TSA.

Conclusions:

  • Sox4 is essential for TSA-induced PUMA expression in a p53-independent pathway.
  • Sox4 plays a critical role in mediating p53-independent apoptotic cell death.
  • This study identifies Sox4 as a key regulator in TSA-induced apoptosis via PUMA.
Keywords:
DBDDNA binding domainPUMATADTSATarget geneTranscription factor Sox4p53-Independent apoptotic cell deathtransactivation domaintrichostatin A

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