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Updated: Apr 20, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
USP11 regulates p53 stability by deubiquitinating p53
Jia-ying Ke1, Cong-jie Dai, Wen-lin Wu
1College of Chemistry and Life Science, Quanzhou Normal University, Quanzhou 36200, China; The Higher Educational Key Laboratory for Molecular Biology and Pharmacology of Fujian Province, Quanzhou 36200, China; Xiamen Women and Children Health Hospital, Xiamen 361005, China; Shouguang People's Hospital, Shouguang 262700, China; Department of Orthopedics, Central Hospital of Zibo, Zibo 255000, China; Department of Pathology, University of Chicago, Chicago 60102, Illinois, USA; Department of Pathology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 36200, China.
Abstract:
The p53 tumor suppressor protein coordinates the cellular responses to a broad range of cellular stresses, leading to DNA repair, cell cycle arrest or apoptosis. The stability of p53 is essential for its tumor suppressor function, which is tightly controlled by ubiquitin-dependent degradation primarily through its negative regulator murine double minute 2 (Mdm2). To better understand the regulation of p53, we tested the interaction between p53 and USP11 using co-immunoprecipitation. The results show that USP11, an ubiquitin-specific protease, forms specific complexes with p53 and stabilizes p53 by deubiquitinating it. Moreover, down-regulation of USP11 dramatically attenuated p53 induction in response to DNA damage stress. These findings reveal that USP11 is a novel regulator of p53, which is required for p53 activation in response to DNA damage.
Insights
Ubiquitin-specific protease 11 (USP11) stabilizes the p53 tumor suppressor protein by removing ubiquitin tags. USP11 is crucial for activating p53 in response to DNA damage.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Stress Response
Background:
- p53 is a critical tumor suppressor protein.
- p53 stability is regulated by ubiquitin-dependent degradation, mainly via Mdm2.
- Understanding p53 regulation is key to cancer research.
Purpose of the Study:
- To investigate the interaction between p53 and USP11.
- To determine USP11's role in p53 stability and function.
Main Methods:
- Co-immunoprecipitation assays were used to test p53-USP11 interaction.
- Ubiquitin-specific protease activity was assessed.
- p53 induction was measured following USP11 down-regulation.
Main Results:
- USP11 forms specific complexes with p53.
- USP11 stabilizes p53 through deubiquitination.
- Down-regulation of USP11 impairs p53 induction after DNA damage.
Conclusions:
- USP11 is a novel regulator of p53.
- USP11 is essential for p53 activation in response to DNA damage.
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