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Published on: August 4, 2019

PML enhances the regulation of p53 by CK1 in response to DNA damage

O Alsheich-Bartok1, S Haupt, I Alkalay-Snir

  • 1Department of Immunology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.

Oncogene
|February 5, 2008
PubMed

Insights

Promyelocytic leukemia protein (PML) enhances stress-induced p53 phosphorylation at Thr18 by recruiting casein kinase 1 (CK1). This action protects p53 from Mdm2 degradation, promoting its activation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Stress and DNA damage trigger p53 accumulation and activation for growth inhibition.
  • p53 activity is regulated by negative regulators Mdm2 and Mdm4.
  • Phosphorylation of p53 at Thr18 is crucial for releasing it from Mdm2/4 inhibition.

Purpose of the Study:

  • To investigate the role of promyelocytic leukemia protein (PML) in regulating p53 Thr18 phosphorylation.
  • To elucidate the mechanism by which PML influences p53 regulation by casein kinase 1 (CK1).

Main Methods:

  • Studied endogenous p53 phosphorylation at Thr18 in response to stress.
  • Assessed the localization and interaction of p53, PML, and CK1 following DNA damage.
  • Utilized CK1 inhibition to evaluate its impact on PML-mediated p53 protection.

Main Results:

  • PML enhances endogenous p53 Thr18 phosphorylation under stress conditions.
  • DNA damage induces nuclear accumulation and interaction of CK1 with p53 and PML.
  • CK1 inhibition disrupts PML's protective effect on p53 against Mdm2-mediated degradation.

Conclusions:

  • PML plays a significant role in regulating p53 phosphorylation by CK1.
  • PML facilitates p53 activation by recruiting p53 and CK1 to PML nuclear bodies, preventing Mdm2 inhibition.

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