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Chromatin remodelling protein SMAR1 inhibits p53 dependent transactivation by regulating acetyl transferase p300

Surajit Sinha1, Sunil Kumar Malonia, Smriti P K Mittal

  • 1National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India.

The International Journal of Biochemistry & Cell Biology
|November 15, 2011
PubMed

Insights

Chromatin remodelling protein SMAR1 inhibits apoptosis by blocking p53 acetylation and p300 expression. SMAR1 interacts with the p53-p300 complex, impacting DNA damage response and apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p53 acetylation is crucial for its function in apoptosis induction following DNA damage.
  • The interplay between p53, p300, and chromatin modifiers is critical in DNA damage response pathways.

Purpose of the Study:

  • To investigate the role of SMAR1 in regulating p53 acetylation and apoptosis.
  • To elucidate the mechanism by which SMAR1 affects the p53-p300 transcriptional complex.

Main Methods:

  • Western blotting to assess protein levels and acetylation status.
  • Co-immunoprecipitation to study protein-protein interactions.
  • Analysis of gene and miRNA expression levels.

Main Results:

  • SMAR1 represses p300 expression, thereby inhibiting p53 acetylation and apoptosis.
  • SMAR1 directly interacts with the p53-p300 complex, antagonizing p53-p300 interaction.
  • Proteasomal inhibitors relieve SMAR1-mediated repression of p300.
  • SMAR1 knockdown enhances p53 acetylation and apoptosis, while p300 overexpression rescues SMAR1's inhibitory effects.

Conclusions:

  • SMAR1 acts as a negative regulator in the p53-mediated DNA damage response pathway.
  • SMAR1 influences apoptosis through modulation of p300 expression and interaction with the p53-p300 complex.
  • SMAR1's role in apoptosis may involve transcription-independent mechanisms.

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