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Molecular and Cellular Biology, December 1999, p. 8383-8392, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Charlotte L. Bevan,1,dagger Sue Hoare,1 Frank Claessens,2 David M. Heery,1,Dagger and Malcolm G. Parker1,*

Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom,1 and Afdeling Biochemie, Campus Gasthuisberg, 300 Leuven, Belgium2

Received 20 May 1999/Returned for modification 23 June 1999/Accepted 14 September 1999

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.

* Corresponding author. Mailing address: Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom. Phone: 44 171 269 3280. Fax: 44 171 269 3094. E-mail: m.parker{at}icrf.icnet.uk.

dagger Present address: Prostate Cancer Research Group, Department of Cancer Medicine, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom.

Dagger Present address: Department of Biochemistry, University of Leicester, Leicester LE1 7RH, United Kingdom.

Molecular and Cellular Biology, December 1999, p. 8383-8392, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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