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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

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Protein phosphatase 1 inhibits p53 signaling by dephosphorylating and stabilizing Mdmx

Zengxin Lu1, Guohui Wan, Huarong Guo

  • 1Department of Radiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, China.

Cellular Signalling
|January 2, 2013
PubMed

Insights

Protein phosphatase 1 (PP1) stabilizes Mdmx by dephosphorylating it, which inhibits the tumor suppressor p53. This finding reveals PP1 as a key regulator in the DNA damage response pathway.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The p53 protein is crucial for DNA damage response and its levels are tightly regulated by posttranslational modifications.
  • Mdmx is a key regulator that inhibits p53 transcriptional activity and is destabilized upon DNA damage through phosphorylation.
  • Previous studies identified Ser342, Ser367, and Ser403 as Mdmx phosphorylation sites.

Purpose of the Study:

  • To identify novel regulators of the p53 signaling pathway.
  • To investigate the role of protein phosphatase 1 (PP1) in the regulation of Mdmx and p53.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • In vitro phosphatase assays to determine dephosphorylation activity.
  • Western blotting to analyze protein levels and phosphorylation status.

Main Results:

  • Protein phosphatase 1 (PP1) directly interacts with Mdmx.
  • PP1 specifically dephosphorylates Mdmx at Ser367.
  • Dephosphorylation of Mdmx by PP1 increases Mdmx stability, leading to inhibition of p53 activity.

Conclusions:

  • PP1 acts as a negative regulator in the p53 signaling pathway.
  • PP1-mediated dephosphorylation of Mdmx is a critical mechanism for controlling p53 activity.
  • PP1 is a significant component of the ATM-Chk2-p53 signaling cascade.

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