Hormonal control of androgen receptor function through SIRT1 Academic Article uri icon

Overview

MeSH Major

  • Dihydrotestosterone
  • Gene Expression Regulation
  • Prostatic Neoplasms
  • Receptors, Androgen
  • Sirtuins

abstract

  • The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.

publication date

  • November 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1636736

Digital Object Identifier (DOI)

  • 10.1128/MCB.00289-06

PubMed ID

  • 16923962

Additional Document Info

start page

  • 8122

end page

  • 35

volume

  • 26

number

  • 21