Regulation of AR Degradation and Function by Ubiquitylation

Abstract

Pathways that mediate the ubiquitin dependent degradation of androgen receptor (AR) remain to be established, and it is apparent that ubiquitylation regulates AR functions in addition to the degradation of unliganded AR. We hypothesize that there are distinct ubiquitin ligases and pathways regulating the degradation and transcriptional functions of liganded nuclear AR versus the unliganded cytoplasmic AR. One of our major objectives is to identify such pathways mediating the turnover of liganded nuclear AR, as these may be exploited therapeutically through the development of selective AR antagonists. Our approach has been to use initially mass spectrometry and identify AR sites that undergo ubiquitylation in the presence and absence of androgen. We have now identified a series of such sites, and current efforts are focused on determining the functional significance of these sites.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2014
Accession Number
ADA615205

Entities

People

  • Steven P Balk

Organizations

  • Beth Israel Deaconess Medical Center

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Degradation
  • Inhibitors
  • Liquid Chromatography
  • Mass Spectrometry
  • Neoplasms
  • Phosphorylation
  • Prostate Cancer
  • Proteins
  • Regulations
  • Spectrometry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Prostate Cancer Biology.