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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Regulation of the sequence-specific DNA binding function of p53 by protein kinase C and protein phosphatases

I Takenaka1, F Morin, B R Seizinger

  • 1Department of Molecular Genetics and Cell Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.

The Journal of Biological Chemistry
|March 10, 1995
PubMed

Insights

The p53 tumor suppressor protein

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The p53 protein acts as a tumor suppressor by regulating cell growth.
  • Its DNA binding activity is crucial for its growth-inhibitory function.
  • p53 activation involves allosteric mechanisms and a negative regulatory domain.

Purpose of the Study:

  • To investigate the role of phosphorylation in regulating p53 DNA binding activity.
  • To identify the specific site and enzymes involved in p53 regulation.
  • To elucidate the reversible nature of p53 activation and its implications for tumor suppression.

Main Methods:

  • Utilized antibody PAb421 to detect the latent form of p53.
  • Investigated the effect of protein kinase C (PKC) phosphorylation on p53.
  • Examined the role of protein phosphatases 1 (PP1) and 2A (PP2A) in dephosphorylation.
  • Assessed changes in DNA binding activity and PAb421 reactivity.

Main Results:

  • Phosphorylation of serine 378 by PKC inactivates the latent p53 form, reducing PAb421 reactivity.
  • This phosphorylation event activates p53's sequence-specific DNA binding.
  • Dephosphorylation by PP1 and PP2A reverses these effects, restoring latent p53 and inhibiting DNA binding.

Conclusions:

  • p53 activity is regulated by reversible phosphorylation at serine 378.
  • Protein kinase C and phosphatases PP1/PP2A act as key regulators of p53's latent and active states.
  • This reversible enzymatic modification provides a mechanism for controlling p53's tumor suppressor function.

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