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USP2a activation of MYC in prostate cancer

William G Nelson1, Angelo M De Marzo, Srinivasan Yegnasubramanian

  • 1Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. bnelson@jhmi.edu

Cancer Discovery
|May 16, 2012
PubMed

Insights

Ubiquitin-specific protease 2a increases MYC oncoprotein levels in prostate cancer by stabilizing MDM2. This disrupts tumor suppressor p53

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MYC oncoprotein overexpression is a driver in many cancers, including prostate cancer.
  • The p53 tumor suppressor pathway regulates microRNAs (miRNAs) that can target MYC mRNA for degradation.
  • Deubiquitinating enzymes play roles in cancer by regulating protein stability.

Purpose of the Study:

  • To investigate the role of ubiquitin-specific protease 2a (USP2a) in regulating MYC levels in prostate cancer.
  • To elucidate the mechanism by which USP2a affects MYC expression and its impact on the p53 pathway.

Main Methods:

  • Prostate cancer cell lines were used to study USP2a and MYC expression.
  • Western blotting and quantitative real-time PCR were employed to assess protein and mRNA levels.
  • Immunoprecipitation assays were performed to investigate protein-protein interactions.

Main Results:

  • USP2a deubiquitinating enzyme was found to be upregulated in prostate cancer cells.
  • USP2a directly interacts with and stabilizes MDM2, an E3 ubiquitin ligase.
  • USP2a-mediated MDM2 stabilization leads to increased MYC protein levels and decreased levels of MYC-targeting miRNAs.

Conclusions:

  • USP2a promotes prostate cancer progression by elevating MYC levels through MDM2 stabilization.
  • USP2a interferes with p53-mediated regulation of MYC via miRNAs, highlighting a novel oncogenic mechanism.
  • Targeting USP2a may represent a therapeutic strategy for prostate cancer.

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