Related Experiment Video
Updated: Jun 16, 2026
10:55
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
USP10 regulates p53 localization and stability by deubiquitinating p53
Jian Yuan1, Kuntian Luo, Lizhi Zhang
1Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Cell
|January 26, 2010
Summary
USP10 deubiquitinates p53, reversing Mdm2-induced degradation and nuclear export. This cytoplasmic protease stabilizes p53 after DNA damage, suppressing tumor growth and offering a new target for wild-type p53 cancers.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- p53 protein stability and localization are critical for its tumor suppressor activity.
- Mdm2-mediated ubiquitination is the primary regulator of p53, inducing its nuclear export and degradation.
- The fate of ubiquitinated cytoplasmic p53 remains largely unknown.
Purpose of the Study:
- To investigate the role of USP10 in regulating p53.
- To elucidate the mechanism by which USP10 affects p53 stability and localization.
- To determine the functional significance of USP10 in cancer.
Main Methods:
- Ubiquitin-specific protease assays
- Western blotting to assess protein levels and modifications
- Immunofluorescence to track protein localization
- Cell proliferation assays
- Analysis of USP10 expression in clear cell carcinomas
Main Results:
- USP10, a cytoplasmic deubiquitinating enzyme, removes ubiquitin from p53.
- USP10 reverses Mdm2-induced nuclear export and degradation of p53.
- USP10 is stabilized and translocates to the nucleus after DNA damage, activating p53.
- ATM-mediated phosphorylation of USP10 at Thr42 and Ser337 regulates its translocation and stabilization.
- USP10 suppresses tumor cell growth in wild-type p53 cells.
- USP10 is downregulated in clear cell carcinomas with wild-type p53.
Conclusions:
- USP10 is a novel regulator of p53 stability and localization.
- USP10 deubiquitination of p53 counteracts Mdm2-mediated regulation.
- USP10 activation of p53 after DNA damage inhibits tumor growth.
- USP10 represents a potential therapeutic target for cancers with wild-type p53.
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...