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Updated: Feb 16, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.8K

BTK blocks the inhibitory effects of MDM2 on p53 activity

Miran Rada1, Mohammad Althubiti1,2, Akang E Ekpenyong-Akiba1

  • 1Department of Molecular and Cell Biology, Mechanisms of Cancer and Aging Laboratory, University of Leicester, Leicester, UK.

Oncotarget
|January 2, 2018
PubMed

Insights

Bruton's Tyrosine Kinase (BTK) disrupts the MDM2-p53 feedback loop by inactivating MDM2. BTK phosphorylation of MDM2 reduces MDM2's ubiquitination activity, enhancing tumor suppressor p53 function.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • p53 is a crucial tumor suppressor regulated by post-translational modifications, including MDM2-mediated ubiquitination and degradation.
  • Bruton's Tyrosine Kinase (BTK) has been shown to increase p53 protein levels and activity via phosphorylation.

Purpose of the Study:

  • To elucidate the mechanisms by which BTK influences p53 regulation, specifically its interaction with MDM2.
  • To investigate the role of BTK in the MDM2-p53 negative feedback loop.

Main Methods:

  • Western blotting to assess protein levels and phosphorylation.
  • Co-immunoprecipitation to study protein-protein interactions.
  • Functional assays to evaluate p53 transcriptional activity and MDM2 ubiquitination activity.

Main Results:

  • BTK expression increases MDM2 levels and is required for MDM2 upregulation after DNA damage.
  • BTK binds to MDM2 and induces its phosphorylation, leading to reduced MDM2 ubiquitination activity.
  • BTK kinase activity disrupts the MDM2-p53 negative feedback loop, enhancing p53 tumor suppressor functions.

Conclusions:

  • BTK's kinase activity is critical for modulating p53 stability and function by directly interfering with MDM2.
  • BTK inactivates MDM2 through phosphorylation, thereby disrupting the negative feedback loop that limits p53 activity.
  • This study reveals a novel mechanism for BTK in cancer, highlighting its role in p53 pathway regulation.
Keywords:
BTKMDM2p53phosphorylationubiquitination

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