Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 213, Issue 1, Pages 79-85Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2003.10.036
Keywords
coactivators and corepressors on androgen receptor; ligand; cofactor recruitment
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The human androgen receptor (AR) is a member of the nuclear hormone receptor superfamily. However, in contrast to other members of this family the amino-(N)-terminus of AR harbors the major transactivation function. Previously we have shown that hormone antagonists that bind to the carboxy-terminal ligand-binding domain repress AR through recruitment of corepressors that are recruited to the receptor N-terminus. Here we show by a modified mammalian two-hybrid system that both the AR interacting domains of the coactivator SRCl and of the corepressor SMRT compete for interaction with the AR N-terminus. In contrast to other members of the nuclear receptor superfamily the LXXLL motifs of SRCle are not required for this interaction, instead a stretch of 135 amino acids of the glutamine rich region (Qr) of SRCle is essential to bind to the AR N-terminus. We show that the Qr-region of SRCl is able to inhibit the interaction of SMRT with AR. Also, we demonstrate that the corepressor mediated repression decreases the antagonist-induced transactivation while, surprisingly, it increases the agonist-induced transactivation. This may indicate that coactivators and corepressors act in concert to dictate the overall receptor-mediated action dependent on the type of ligand. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
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