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Ubiquitin-specific protease 14 promotes prostate cancer progression through deubiquitinating the transcriptional

Lin Geng1, Xing Chen1, Meng Zhang1

  • 1Department of Urology, China-Japan Friendship Hospital, No. 2 Yinghua Dongjie, Chaoyang District, Beijing, 100029, China.

Biochemical and Biophysical Research Communications
|January 23, 2020
PubMed

Insights

Ubiquitin-specific protease 14 (USP14) stabilizes Activating Transcription Factor 2 (ATF2), promoting prostate cancer cell growth. Inhibiting USP14 could be a new therapeutic strategy for prostate cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Activating Transcription Factor 2 (ATF2) is an oncogene in prostate cancer.
  • ATF2 is regulated by the CUL3-SPOP-RBX1 E3 ubiquitin ligase complex, and SPOP mutations are common in prostate cancer.
  • The deubiquitinating enzyme responsible for ATF2 stabilization remained unidentified.

Purpose of the Study:

  • To identify the deubiquitinating enzyme that stabilizes ATF2.
  • To investigate the role of this enzyme in prostate cancer progression.
  • To explore the potential of targeting this enzyme as a therapeutic strategy.

Main Methods:

  • Co-immunoprecipitation assays to identify ATF2-interacting proteins.
  • Western blotting to assess ATF2 protein levels and ubiquitination.
  • Pharmacological inhibition and siRNA-mediated depletion of USP14.
  • Cell proliferation assays (in vitro and in vivo).
  • ATF2 gene silencing experiments.

Main Results:

  • ATF2 was found to associate with ubiquitin-specific protease 14 (USP14).
  • USP14 increases ATF2 protein abundance and transcriptional activity.
  • USP14 inhibition or depletion reduces ATF2 levels and activity, inhibiting prostate cancer cell proliferation.
  • Silencing ATF2 counteracted USP14-mediated proliferation.

Conclusions:

  • USP14 deubiquitinates and activates ATF2, promoting prostate cancer cell proliferation.
  • The USP14-ATF2 axis is critical for prostate cancer progression.
  • USP14 inhibition represents a potential therapeutic approach for prostate cancer.
Keywords:
ATF2DeubiquitinationProstate cancerUSP14

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