Related Experiment Video

Updated: Nov 9, 2025

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
09:40

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells

Published on: November 2, 2017

7.5K

Bimodal regulation of the PRC2 complex by USP7 underlies tumorigenesis

Dongxue Su1,2, Wenjuan Wang1, Yongqiang Hou2,3

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

Nucleic Acids Research
|April 13, 2021
PubMed

Insights

Ubiquitin-specific protease 7 (USP7) stabilizes EZH2, a key cancer protein, by deubiquitination. This USP7/EZH2 complex drives cancer growth and progression, highlighting USP7 as a potential therapeutic target.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Overexpression of EZH2 (Enhancer of Zeste Homolog 2), a subunit of Polycomb Repressive Complex 2 (PRC2), is common in various cancers.
  • The precise regulation of EZH2 abundance and function in cancer remains unclear.

Purpose of the Study:

  • To investigate the regulatory relationship between USP7 (Ubiquitin-Specific Protease 7) and EZH2 in cancer cells.
  • To elucidate the role of USP7 in EZH2 stability, PRC2 activity, and cancer progression.

Main Methods:

  • Co-immunoprecipitation to confirm physical association between USP7 and PRC2/EZH2.
  • Western blotting to assess protein levels and ubiquitination status (H2BK120ub1, H2AK119ub1).
  • Genome-wide analysis to identify transcriptional targets of the USP7/PRC2 complex.
  • In vitro and in vivo assays to evaluate the impact on cancer cell proliferation and tumorigenesis.

Main Results:

  • USP7 physically associates with PRC2 and deubiquitinates EZH2, thereby stabilizing it.
  • USP7-mediated H2BK120ub1 deubiquitination is essential for PRC2 chromatin loading and H3K27 trimethylation.
  • The USP7/PRC2 complex targets genes involved in cell growth, such as FOXO1, promoting cancer proliferation and tumorigenesis.
  • Elevated USP7 and EZH2 expression correlates with tumor progression, reduced FOXO1 levels, higher histological grades, and poorer patient prognosis.

Conclusions:

  • USP7 plays a dual role in regulating EZH2 abundance and function, critical for cancer cell proliferation.
  • The USP7/EZH2 axis represents a promising therapeutic target for cancer intervention.

More Related Videos

Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

60.9K
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

11.1K

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...
4.8K
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.
37.2K
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....
8.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.0K
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...
6.8K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.9K