The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1

The androgen receptor is unusual among nuclear receptors in that most, if n ot all, of its activity is mediated via the constitutive activation functio n in the N terminus. Here we demonstrate that p160 coactivators such as SRC 1 (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 li gand-binding domain by means of LXXLL motifs, this interaction is not essen tial since an SRC1 mutant with no functional LXXLL motifs retains its abili ty to potentiate androgen receptor activity. In contrast, mutants lacking t he 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 es trogen receptor, which requires interaction with the ligand-binding domain.