Posttranslational modification of the androgen receptor in prostate cancer

Int J Mol Sci. 2013 Jul 16;14(7):14833-59. doi: 10.3390/ijms140714833.

Abstract

The androgen receptor (AR) is important in the development of the prostate by regulating transcription, cellular proliferation, and apoptosis. AR undergoes posttranslational modifications that alter its transcription activity, translocation to the nucleus and stability. The posttranslational modifications that regulate these events are of utmost importance to understand the functional role of AR and its activity. The majority of these modifications occur in the activation function-1 (AF1) region of the AR, which contains the transcriptional activation unit 1 (TAU1) and 5 (TAU5). Identification of the modifications that occur to these regions may increase our understanding of AR activation in prostate cancer and the role of AR in the progression from androgen-dependent to castration-resistant prostate cancer (CRPC). Most of the posttranslational modifications identified to date have been determined using the full-length AR in androgen dependent cells. Further investigations into the role of posttranslational modifications in androgen-independent activation of full-length AR and constitutively active splicing variants are warranted, findings from which may provide new therapeutic options for CRPC.

Publication types

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

MeSH terms

  • Acetylation
  • Humans
  • Male
  • Methylation
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Sumoylation
  • Ubiquitination

Substances

  • Receptors, Androgen
  • Phosphoric Monoester Hydrolases