Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH2-terminal domain

Bin He, Jon A. Kemppainen, Johannes J. Voegel, Hinrich Gronemeyer, Elizabeth M. Wilson

Research output: Contribution to journalArticle

271 Scopus citations

Abstract

Activation function 2 in the ligand binding domain of nuclear receptors forms a hydrophobic cleft that binds the LXXLL motif of p160 transcriptional coactivators. Here we provide evidence that activation function 2 in the androgen receptor serves as the contact site for the androgen dependent NH2- and carboxyl-terminal interaction of the androgen receptor and only weakly interacts with p160 coactivators in an LXXLL-dependent manner. Mutagenesis studies indicate that it is the NH2-/carboxyl-terminal interaction that is required by activation function 2 to stabilize helix 12 and slow androgen dissociation critical for androgen receptor activity in vivo. The androgen receptor recruits p160 coactivators through its NH2-terminal and DNA binding domains in an LXXLL motif-independent manner. The results suggest a novel function for activation function 2 and a unique mechanism of nuclear receptor transactivation.

Original languageEnglish (US)
Pages (from-to)37219-37225
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number52
DOIs
StatePublished - Dec 24 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH<sub>2</sub>-terminal domain'. Together they form a unique fingerprint.

Cite this