Related Experiment Video
Updated: Feb 24, 2026
10:55
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
2.8K
USP3 stabilizes p53 protein through its deubiquitinase activity
Song Fu1, Shize Shao1, Longqiang Wang1
1Department of Spine and Spinal Cord Surgery, Wendeng Orthopaedic Hospital, Weihai, Shandong, 264400, PR China.
Biochemical and Biophysical Research Communications
|August 16, 2017
Summary
USP3 deubiquitinase regulates the stability of the tumor suppressor p53 (the guardian of the genome). USP3 depletion accelerates p53 degradation, promoting cell proliferation and transformation, while its reconstitution inhibits these processes.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- p53 is a critical tumor suppressor, acting as the guardian of genome integrity.
- The stability of p53 protein is tightly regulated, primarily through degradation mediated by MDM2.
Purpose of the Study:
- To investigate the role of USP3 in regulating p53 stability and its impact on normal cell transformation.
- To determine if USP3's enzymatic activity is essential for its function in p53 regulation.
Main Methods:
- Co-immunoprecipitation assays to assess USP3-p53 interaction.
- Western blotting to analyze p53 protein levels upon USP3 depletion or reconstitution.
- Cell proliferation and transformation assays.
Main Results:
- USP3 was found to interact with p53 and regulate its stability.
- Depletion of USP3 led to accelerated p53 degradation, enhanced cell proliferation, and transformation.
- Reconstitution with wildtype USP3, but not a catalytically inactive mutant (USP3 C168S), restored p53 stability and inhibited cell proliferation and transformation.
Conclusions:
- USP3 is a novel regulator of p53 stability.
- USP3's deubiquitinase activity is crucial for maintaining p53 stability and suppressing normal cell transformation.
Related Concept Videos
02:23Abnormal Proliferation
5.3K
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...
5.3K
02:04Covalently Linked Protein Regulators
9.8K
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....
9.8K
02:58Regulated Protein Degradation
9.0K
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...
9.0K
02:58Regulated Protein Degradation
3.2K
3.2K
01:37The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
01:23Negative Regulator Molecules
38.6K
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.
38.6K