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Updated: Jul 9, 2025

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
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Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2

Yushu Xing1,2, Jirimu Ba-Tu3, Chongyang Dong4

  • 1College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

Cell Death & Disease
|November 29, 2023
PubMed

Insights

Ubiquitin-specific peptidase 27X (USP27X) stabilizes Chromobox protein homolog 2 (CBX2) in aggressive cancers. This GSK3β-USP27X-CBX2 axis promotes breast cancer progression, with high USP27X and CBX2 indicating poor prognosis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Chromobox protein homolog 2 (CBX2) is implicated in aggressive cancer progression.
  • The regulation of CBX2 by deubiquitinating enzymes is not well understood.
  • Proteasome-dependent pathways are key to CBX2 modulation.

Purpose of the Study:

  • To identify deubiquitinating enzymes targeting CBX2.
  • To elucidate the regulatory mechanism of CBX2 by USP27X.
  • To investigate the role of the GSK3β-USP27X-CBX2 axis in breast cancer.

Main Methods:

  • Mass spectrometry to identify USP27X as a CBX2-targeting deubiquitinating enzyme.
  • Analysis of USP27X overexpression and deficiency effects on CBX2 levels and tumorigenesis.
  • Investigation of GSK3β interaction and phosphorylation of USP27X.
  • Clinical correlation analysis of USP27X and CBX2 expression in breast cancer tissues.

Main Results:

  • USP27X deubiquitinates and stabilizes CBX2, enhancing its levels.
  • USP27X deficiency leads to CBX2 degradation and inhibits tumorigenesis.
  • GSK3β phosphorylates USP27X, strengthening the USP27X-CBX2 interaction and CBX2 stability.
  • High co-expression of USP27X and CBX2 correlates with poor prognosis in breast cancer patients.

Conclusions:

  • USP27X is a critical regulator of CBX2 stability and function in cancer.
  • The GSK3β-USP27X-CBX2 signaling axis drives malignant progression in breast cancer.
  • USP27X and CBX2 represent potential therapeutic targets for breast cancer treatment.

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