Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TIF2

Mol Cell Endocrinol. 2006 Mar 9;247(1-2):150-65. doi: 10.1016/j.mce.2005.12.052. Epub 2006 Feb 15.

Abstract

We previously reported that testicular zinc finger protein (TZF) is a corepressor for androgen receptor (AR). The present study demonstrated that a central portion (amino acids 512-663) of TZF, TZF(512-663), is responsible for both binding to AR and repressing the transactivation. TZF recruited endogenous histone deacetylase 2 (HDAC2) and formed a complex with agonist-bound AR. Imaging analyses showed that TZF and TZF(512-663) were recruited by AR and simultaneously impaired distinct AR foci formation. Quantification of the foci number using a three-dimensional imaging method revealed that the number of intranuclear AR foci was related to its transactivation activity. Moreover, increased levels of TZF dissociated a coactivator, TIF2, from the AR foci and vice versa. These results indicate that the ligand-dependent transactivation function of AR is quantitatively related to its intranuclear foci formation, and suggest that corepressors, such as TZF, act on these intranuclear events competitively with coactivators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha-Dihydroprogesterone / pharmacology
  • Androgens
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Histone Deacetylase 2
  • Histone Deacetylases / metabolism*
  • Humans
  • Male
  • Mice
  • Mutation
  • Nuclear Receptor Coactivator 2 / metabolism*
  • Protein Binding
  • Receptors, Androgen / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcriptional Activation*

Substances

  • Androgens
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Receptors, Androgen
  • Repressor Proteins
  • Rog protein, mouse
  • TZFP protein, human
  • 5-alpha-Dihydroprogesterone
  • Hdac2 protein, mouse
  • Histone Deacetylase 2
  • Histone Deacetylases