Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9379-84. doi: 10.1073/pnas.0900258106. Epub 2009 May 20.

Identification of betaArrestin2 as a corepressor of androgen receptor signaling in prostate cancer.

Author information

  • 1Department of Pathology, Medical College of Georgia, Augusta, GA 30912, USA.

Abstract

Androgen receptor (AR) signaling regulates the development and homeostasis of male reproductive organs, including the prostate. Deregulation of AR and AR coregulators, expression, or activity is involved in the initiation of prostate cancer and contributes to the transition of the disease to hormone-refractory stage. The ubiquitous betaArrestin proteins are now recognized as bona fide adapters and signal transducers with target effectors found in both the cytosol and nucleus. Here, we provide evidence that betaArrestin2 forms a complex with AR and acts as an AR corepressor in androgen-dependent prostate cancer cells. Accordingly, the forced overexpression of betaArrestin2 diminishes, and knockdown of betaArrestin2 expression with RNAi increases the androgen-induced prostate-specific antigen (PSA) gene expression. betaArrestin2 serves as an adapter, bringing into close proximity the Mdm2 E3 ligase and AR, thereby promoting AR ubiquitylation and degradation. Human prostate tissues evidence an inverse relationship between the expression of betaArrestin2 and AR activity: glands that express high levels of betaArrestin2 exhibit low expression of PSA, and those glands that express low levels of betaArrestin2 evidence elevated PSA levels. We conclude that betaArrestin2 acts as a corepressor of AR by serving as a scaffold for Mdm2 leading to the AR ubiquitylation and degradation.

PMID:
19458261
[PubMed - indexed for MEDLINE]
PMCID:
PMC2695075
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk