Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination

Cancer Cell. 2009 Apr 7;15(4):270-82. doi: 10.1016/j.ccr.2009.02.021.


The androgen receptor (AR) plays a critical role in prostate cancer. We have identified a ubiquitin E3 ligase, RNF6, as an AR-associated protein in a proteomic screen. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of RNF6 or mutation of RNF6-induced ubiquitination acceptor sites on AR selectively alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen-responsive elements present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our data suggest that RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Androgens / pharmacology
  • Animals
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Kidney / cytology
  • Kidney / metabolism
  • Male
  • Molecular Sequence Data
  • Neoplasms, Hormone-Dependent
  • Prostatic Hyperplasia
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*
  • Ubiquitination*


  • AR protein, human
  • Androgens
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNF6 protein, human
  • Receptors, Androgen

Associated data

  • GEO/GSE14575