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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

The GAS41-PP2Cbeta complex dephosphorylates p53 at serine 366 and regulates its stability

Jeong Hyeon Park1, Rebecca J Smith, Sheau-Yann Shieh

  • 1Institute of Molecular Biosciences, Massey University, Palmerston North 4442, New Zealand. J.Park@massey.ac.nz

The Journal of Biological Chemistry
|February 15, 2011
PubMed

Insights

The GAS41-PP2Cβ complex, not PP2Cβ alone, dephosphorylates serine 366 on the p53 tumor suppressor. This complex enhances cell survival after DNA damage and may drive glioma oncogenesis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • The p53 tumor suppressor protein is crucial for cellular response to DNA damage.
  • p53 regulation involves post-translational modifications, including phosphorylation and proteasomal degradation.
  • Counteracting phosphatases that regulate p53 activity remain largely uncharacterized.

Purpose of the Study:

  • To identify phosphatases involved in p53 regulation.
  • To investigate the role of the GAS41-PP2Cβ complex in p53 dephosphorylation.
  • To elucidate the functional consequences of GAS41-PP2Cβ activity on cell survival and potential oncogenic mechanisms.

Main Methods:

  • Co-immunoprecipitation to identify interacting partners.
  • In vitro phosphatase assays to determine substrate specificity.
  • Cellular assays measuring p53 levels and cell survival after UV irradiation.
  • Analysis of GAS41 amplification in human glioma datasets.

Main Results:

  • The complex of GAS41 and PP2Cβ specifically dephosphorylates serine 366 on p53.
  • PP2Cβ alone does not dephosphorylate p53 at this site.
  • Ectopic expression of GAS41 and PP2Cβ reduces UV-induced p53 accumulation.
  • Overexpression of GAS41 and PP2Cβ enhances cell survival following genotoxic stress.
  • GAS41 amplification is observed in human gliomas.

Conclusions:

  • The GAS41-PP2Cβ complex is the first identified regulator of p53 serine 366 dephosphorylation.
  • This complex provides a novel mechanism for controlling p53 activity and promoting cell survival.
  • GAS41's role in p53 dephosphorylation represents a potential oncogenic mechanism in gliomas.

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