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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

p53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation-mediated cellular senescence

Seok Young Jang1, Soo Young Kim, Young-Seuk Bae

  • 1School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.

FEBS Letters
|October 5, 2011
PubMed

Insights

Casein kinase II (CKII) inhibition promotes tumor suppression by stabilizing p53. This occurs through reduced SIRT1 activity, enhancing p53 acetylation and senescence.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Cellular senescence is a key tumor suppression mechanism.
  • p53 activation is essential for senescence induced by CKII inhibition.
  • CKII inhibition leads to p53 acetylation at K382, a modification suppressed by SIRT1 activation.

Purpose of the Study:

  • To elucidate the molecular mechanism by which CKII inhibition induces p53 stabilization and cellular senescence.
  • To investigate the interaction between CKII, SIRT1, and p53 in the context of senescence.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Maltose binding protein pull-down and yeast two-hybrid assays to confirm SIRT1-CKIIβ binding.
  • In vitro kinase assays to assess CKII phosphorylation of SIRT1.
  • Cellular senescence assays in HCT116 and HEK293 cells.
  • SIRT1 overexpression experiments.

Main Results:

  • CKII inhibition induced p53 acetylation at K382, which was inhibited by SIRT1 activation.
  • SIRT1 directly interacted with CKIIβ, but not CKIIα, independently of p53.
  • CKII inhibition reduced cellular SIRT1 activity.
  • CKII phosphorylated and activated SIRT1 in vitro.
  • SIRT1 overexpression counteracted CKII inhibition-induced senescence.

Conclusions:

  • CKII downregulation stabilizes p53 by negatively regulating SIRT1 deacetylase activity.
  • This regulatory axis (CKII-SIRT1-p53) is critical for mediating cellular senescence and tumor suppression.

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