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Abnormal Proliferation

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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 daughter...

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Interactions Between Signaling Pathways

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Related Experiment Video

Updated: Jun 6, 2026

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

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

Published on: August 4, 2019

REGgamma modulates p53 activity by regulating its cellular localization.

Jian Liu¹, Guowu Yu, Yanyan Zhao

¹Institute of Biomedical Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

Journal of Cell Science

|November 19, 2010

Summary

The proteasome activator REGγ facilitates p53 protein degradation, impacting apoptosis and tumor growth. Inhibiting REGγ reduces tumor progression, highlighting its role in cancer.

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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Area of Science:

Molecular Biology
Cellular Biology
Cancer Research

Background:

The proteasome activator REGγ's role in protein degradation and its mechanisms are not fully understood.
REGγ is known to mediate the degradation of intact mammalian proteins.
Understanding REGγ's function is crucial for deciphering cellular regulatory pathways.

Purpose of the Study:

To elucidate the biological roles and mechanisms of REGγ.
To investigate REGγ's regulation of p53 cellular distribution and degradation.
To assess the impact of REGγ on apoptosis and tumor development.

Main Methods:

Investigated REGγ's effect on p53 monoubiquitylation, nuclear export, and degradation.
Analyzed the influence of REGγ on p53 tetramerization and interaction with HDM2.
Utilized cell-based assays and a mouse xenograft model to study REGγ function.
Assessed the effects of REGγ depletion on stress-induced apoptosis and tumor growth.

Main Results:

REGγ facilitates p53 multiple monoubiquitylation, promoting its nuclear export and degradation.
REGγ inhibits p53 tetramerization, enhancing cytoplasmic relocation and reducing nuclear p53.
REGγ-mediated p53 monoubiquitylation enhances interaction with HDM2, facilitating p53 polyubiquitylation and degradation.
REGγ depletion sensitizes cells to apoptosis and significantly reduces tumor growth in vivo.

Conclusions:

REGγ plays a critical role in controlling apoptosis through p53 regulation.
REGγ-mediated p53 inactivation is a key mechanism in cancer progression.
Targeting REGγ may offer a therapeutic strategy for cancer treatment.