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Updated: Jun 26, 2025

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The deubiquitinating enzyme USP4 regulates BRCA1 stability and function.

Xueyuan Guo1, Yanfang Ma1, Ting Zhang1

  • 1Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

NPJ Breast Cancer
|May 11, 2024
PubMed
Summary
This summary is machine-generated.

The deubiquitinase USP4 stabilizes BRCA1 protein, crucial for DNA repair and suppressing breast cancer. USP4 deficiency impairs repair, increases instability, and correlates with poor patient survival.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • BRCA1 is a tumor suppressor in breast cancer.
  • Protein stability is often regulated by ubiquitination and deubiquitination.
  • The specific deubiquitinating enzyme for BRCA1 was previously undefined.

Purpose of the Study:

  • To identify the deubiquitinating enzyme responsible for BRCA1 regulation.
  • To elucidate the role of this enzyme in DNA repair and cancer suppression.
  • To investigate the clinical relevance of this enzyme in breast and gynecological cancers.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • Western blotting to evaluate protein levels and ubiquitination status.
  • DNA repair assays, cell viability assays, and analysis of patient tumor data.

Main Results:

  • USP4 directly interacts with and deubiquitinates BRCA1, stabilizing its protein level.
  • USP4 knockdown leads to decreased BRCA1, impaired DNA repair, genomic instability, and resistance to DNA-damaging agents and PARP inhibitors.
  • USP4 is downregulated in breast cancer tissues, correlating with poorer patient survival, and harbors loss-of-function mutations in gynecological cancers.

Conclusions:

  • USP4 functions as a deubiquitinase for BRCA1, enhancing its stability and function.
  • USP4 plays a critical role in maintaining genomic integrity and suppressing breast tumorigenesis.
  • USP4 represents a potential therapeutic target in BRCA1-related cancers.