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The Deubiquitinating Enzyme USP7 Regulates Androgen Receptor Activity by Modulating Its Binding to Chromatin

Shu-Ting Chen1, Maiko Okada2, Ryuichiro Nakato1

  • 1From the Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032 and.

The Journal of Biological Chemistry
|July 16, 2015
PubMed

Insights

The deubiquitinating enzyme USP7 is a novel co-regulator of the androgen receptor (AR) in prostate cancer. Inhibiting USP7 may offer a new therapeutic strategy for treating prostate cancer by blocking AR signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The androgen receptor (AR) is crucial in prostate cancer, but current therapies are limited by AR signaling heterogeneity.
  • Understanding AR reactivation mechanisms is vital for developing new prostate cancer treatments.

Purpose of the Study:

  • To identify novel co-regulators of the androgen receptor (AR) involved in prostate cancer.
  • To investigate the role of the deubiquitinating enzyme USP7 in AR transcriptional activity.

Main Methods:

  • Antibody-based affinity purification to identify AR-interacting proteins.
  • Biochemical assays to assess AR deubiquitination and androgen-dependent association.
  • Chromatin immunoprecipitation (ChIP) assays to determine USP7-AR complex formation on target gene promoters.
  • Transcriptome profiling of USP7-knockdown cells.

Main Results:

  • USP7 was identified as a novel AR co-regulator in prostate cancer cells.
  • USP7 associates with AR in an androgen-dependent manner and mediates AR deubiquitination.
  • USP7 facilitates AR binding to chromatin at androgen-responsive elements and is essential for the expression of key androgen-responsive genes.

Conclusions:

  • USP7 plays a critical role in regulating androgen receptor transcriptional activity in prostate cancer.
  • USP7 inhibition represents a promising therapeutic strategy for prostate cancer treatment.
Keywords:
androgen receptorgene transcriptionprostate cancertranscriptional coactivatorubiquitin-dependent protease

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