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Updated: Jun 8, 2026
10:55
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
USP7/HAUSP promotes the sequence-specific DNA binding activity of p53
Feroz Sarkari1, Yi Sheng, Lori Frappier
1Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Plos One
|October 2, 2010
Summary
The ubiquitin specific protease USP7 (Ubiquitin Specific Protease 7) regulates p53
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- p53 is a crucial tumor suppressor that initiates cellular stress responses.
- p53's function as a transcription factor depends on sequence-specific DNA binding.
- Post-translational modifications of p53's C-terminal region regulate its DNA binding activity.
Purpose of the Study:
- To investigate the role of USP7 (Ubiquitin Specific Protease 7) in regulating p53's sequence-specific DNA binding.
- To determine the USP7 domain and activity responsible for p53 regulation.
Main Methods:
- In vitro assays to assess p53 DNA binding activity.
- Interaction studies between USP7 and p53.
- Cellular experiments overexpressing wild-type and catalytically inactive USP7.
- Analysis of p53 target gene expression (e.g., p21).
Main Results:
- USP7 regulates p53's sequence-specific DNA binding in vitro.
- This regulation involves the USP7 C-terminal domain and is independent of its deubiquitylation activity.
- Overexpression of catalytically inactive USP7 enhances p53 binding to target sequences and p21 expression in cells.
- The USP7 C-terminal domain alone is sufficient to induce p21 expression.
Conclusions:
- USP7 regulates p53 DNA binding through a novel mechanism independent of its deubiquitylation function.
- The USP7 C-terminal domain plays a key role in this regulation.
- This finding reveals a new layer of p53 functional control by USP7.
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