Related Experiment Video

Updated: Aug 3, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.2K

VprBP/DCAF1 regulates p53 function and stability through site-specific phosphorylation

Nikhil Baban Ghate1, Sungmin Kim1, Roasa Mehmood1

  • 1Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.

Oncogene
|April 11, 2023
PubMed

Insights

VprBP (Vpr-binding protein) phosphorylates p53 at serine 367, inhibiting its tumor-suppressing activity and promoting cancer growth. This phosphorylation event also targets p53 for degradation, highlighting VprBP as a key regulator in tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • VprBP (DCAF1) is an overexpressed kinase in cancer, linked to gene silencing and tumorigenesis.
  • VprBP's role in histone H2A phosphorylation is established, but its non-histone targets and oncogenic signaling roles are unexplored.

Purpose of the Study:

  • To investigate if VprBP phosphorylates non-histone proteins.
  • To determine the role of VprBP-mediated phosphorylation in oncogenic signaling pathways.
  • To elucidate the mechanism by which VprBP influences p53 function and stability.

Main Methods:

  • Investigated VprBP's interaction with p53.
  • Analyzed the effect of VprBP on p53 phosphorylation at serine 367 (S367p).
  • Assessed the impact of p53S367p on p53 transcriptional activity, growth suppression, and proteasomal degradation.
  • Examined the role of p53 acetylation in regulating VprBP-p53 interaction and p53 function.

Main Results:

  • VprBP directly interacts with p53's C-terminal domain to catalyze p53S367p.
  • VprBP-mediated p53S367p attenuates p53's transcriptional and growth-suppressive activities.
  • p53S367p promotes p53 proteasomal degradation, reducing p53 protein levels and transactivation.
  • p53 acetylation abrogates VprBP-p53 interaction, preventing p53S367p and enhancing p53 function in response to DNA damage.

Conclusions:

  • VprBP acts as a negative regulator of p53 function through S367 phosphorylation.
  • VprBP-mediated p53S367p is a novel mechanism that modulates p53 stability and promotes tumorigenesis.
  • Targeting the VprBP-p53 interaction offers a potential therapeutic strategy for cancer treatment.

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

9.6K
Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

60.6K

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently 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....
6.9K
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...
4.6K
DNA Damage can Stall the Cell Cycle02:37

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...
9.2K
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.
35.5K
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
Regulated Protein Degradation02:58

Regulated 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...
7.4K