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Related Experiment Videos

Histone deacetylases specifically down-regulate p53-dependent gene activation.

L J Juan1, W J Shia, M H Chen

  • 1National Health Research Institutes, 128 Yen-Chiu-Yuan Road, Sec 2, Taipei 115, Taiwan.

The Journal of Biological Chemistry
|April 25, 2000
PubMed
Summary
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Histone deacetylases (HDACs) regulate the tumor suppressor p53 by removing acetyl groups, which reduces p53

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • p53 is a critical tumor suppressor gene frequently mutated in cancer.
  • p53 activity is regulated by posttranslational modifications, including acetylation.
  • Acetylation generally enhances p53 activity, promoting cell cycle arrest or apoptosis.

Purpose of the Study:

  • To investigate the role of mammalian histone deacetylases (HDACs) in regulating p53 function.
  • To determine if HDACs can down-regulate p53 activity through deacetylation.
  • To elucidate the interaction between p53 and HDACs.

Main Methods:

  • Co-expression of HDACs (1, 2, and 3) with p53.
  • Assays to measure p53 acetylation levels and transcriptional activity.

Related Experiment Videos

  • GST pull-down and immunoprecipitation assays to assess protein interactions.
  • In vitro deacetylation assays using p53 peptides and HDAC1.
  • Main Results:

    • HDAC1, HDAC2, and HDAC3 were found to down-regulate p53 function in a dosage-dependent manner.
    • HDAC-mediated down-regulation of p53 requires deacetylase activity and targets specific acetylation sites.
    • p53 directly interacts with HDAC1 both in vitro and in vivo.
    • HDAC1 deacetylated p53 in vitro and reduced p53 acetylation and transcriptional activity in vivo.
    • HDACs reduced p53's activation of the BAX promoter.

    Conclusions:

    • Mammalian HDACs, particularly HDAC1, can deacetylate and inhibit p53 activity.
    • p53 deacetylation by HDACs is a mechanism controlling p53's physiological function.
    • These findings highlight a novel regulatory pathway for the tumor suppressor p53.