The AF1 and AF2 Domains of the Androgen Receptor Interact with Distinct Regions of SRC1

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1999 Nov 24

PMID 10567563

Citations 113

Authors

C L Bevan

S Hoare

F Claessens

D M Heery

M G Parker

Affiliations

Soon will be listed here.

Abstract

The androgen receptor is unusual among nuclear receptors in that most, if not all, of its activity is mediated via the constitutive activation function in the N terminus. Here we demonstrate that p160 coactivators such as SRC1 (steroid receptor coactivator 1) interact directly with the N terminus in a ligand-independent manner via a conserved glutamine-rich region between residues 1053 and 1123. Although SRC1 is capable of interacting with the ligand-binding domain by means of LXXLL motifs, this interaction is not essential since an SRC1 mutant with no functional LXXLL motifs retains its ability to potentiate androgen receptor activity. In contrast, mutants lacking the glutamine-rich region are inactive, indicating that this region is both necessary and sufficient for recruitment of SRC1 to the androgen receptor. This recruitment is in direct contrast to the recruitment of SRC1 to the estrogen receptor, which requires interaction with the ligand-binding domain.

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