Related Experiment Video

Updated: May 5, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.6K

XPC promotes MDM2-mediated degradation of the p53 tumor suppressor

Jing Yan Krzeszinski1, Vitnary Choe, Jia Shao

  • 1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 First Affiliated Hospital, Nanchang University, Jiangxi 330006, People's Republic of China.

Molecular Biology of the Cell
|November 22, 2013
PubMed

Insights

The DNA repair protein XPC regulates the degradation of the tumor suppressor p53 by directly interacting with MDM2. This interaction is crucial for targeting ubiquitylated p53 to the proteasome for destruction.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The ubiquitin receptor Rad23 facilitates p53 proteasomal degradation, but its recognition mechanism for p53 is unknown.
  • Understanding p53 turnover is critical for cancer biology, as p53 is a key tumor suppressor.

Purpose of the Study:

  • To elucidate the role of XPC, a Rad23-binding protein, in the regulation of p53 protein stability and degradation.
  • To investigate the mechanism by which XPC influences p53 turnover and its interaction with the proteasome.

Main Methods:

  • Assessing p53 ubiquitylation and proteasomal association in XPC-deficient cells.
  • Investigating the direct interaction between XPC and MDM2.
  • Analyzing the impact of a pathogenic XPC mutant (W690S) on p53 degradation.

Main Results:

  • XPC deficiency leads to ubiquitylated p53 with reduced proteasomal association, indicating a post-ubiquitylation regulatory role for XPC.
  • XPC directly interacts with MDM2, participating in the MDM2-mediated p53 degradation pathway.
  • The XPC W690S mutant shows impaired MDM2 binding and p53 degradation.
  • XPC overexpression destabilizes p53, while UV irradiation stabilizes it, highlighting XPC's critical regulatory function.

Conclusions:

  • XPC plays a crucial role in regulating p53 protein degradation through its interaction with MDM2.
  • This finding reveals a novel link between DNA repair (XPC) and proteolysis (p53 degradation), impacting cancer cell mechanisms.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

8.9K
Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

5.0K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal 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...
4.0K
DNA Damage Can Stall the Cell Cycle02:36

DNA 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...
2.4K
DNA Damage can Stall the Cell Cycle02:36

DNA 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...
8.5K
Negative Regulator Molecules01:23

Negative 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.
32.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K