Related Experiment Video

Updated: Apr 2, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.9K

USP4 inhibits p53 and NF-κB through deubiquitinating and stabilizing HDAC2

Z Li1,2, Q Hao1,2, J Luo3

  • 1State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, China.

Oncogene
|September 29, 2015
PubMed

Insights

Ubiquitin-specific peptidase 4 (USP4) stabilizes histone deacetylase 2 (HDAC2), impacting cancer-related pathways like p53 and NF-κB. This reveals a new role for USP4 in cancer.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Histone deacetylases (HDACs) are key epigenetic regulators implicated in various human diseases, notably cancers.
  • Understanding HDAC regulation is crucial for developing targeted cancer therapies.
  • HDAC2, a specific HDAC, plays a significant role in cellular processes relevant to cancer.

Purpose of the Study:

  • To investigate the regulatory mechanism of HDAC2 stability.
  • To identify novel interacting partners of HDAC2.
  • To elucidate the functional role of USP4 in HDAC2 regulation and its implications in cancer.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein-protein interactions between USP4 and HDAC2.
  • Western blotting to assess protein levels and acetylation status.
  • Cellular assays to evaluate p53 transcriptional activity and apoptotic responses.
  • NF-κB reporter assays to measure TNFα-induced activation.

Main Results:

  • USP4 directly interacts with and deubiquitinates HDAC2, leading to its stabilization.
  • Overexpression of USP4 results in increased HDAC2 levels, decreased p53 acetylation, and impaired p53-mediated transcriptional activation and apoptosis.
  • USP4 targets HDAC2 to suppress TNFα-induced NF-κB activation.

Conclusions:

  • USP4 deubiquitinates and stabilizes HDAC2, influencing critical cancer-related signaling pathways.
  • USP4's regulation of HDAC2 impacts p53 pathway integrity and NF-κB activation, suggesting a novel tumor-suppressive or oncogenic role in cancer.
  • This study uncovers a new layer of epigenetic regulation involving USP4 and HDAC2, offering potential therapeutic avenues for cancer treatment.

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

10.4K
Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

7.1K

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...
5.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.9K
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....
9.9K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.3K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.9K
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.
39.0K