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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

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
PubMed

Insights

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

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.

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