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 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.
Bevan
C L
CL
Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
Hoare
S
S
Claessens
F
F
Heery
D M
DM
Parker
M G
MG
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D005973:Glutamine / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056918:Nuclear Receptor Coactivators; D000078723:Nuclear Receptor Interacting Protein 1; D015513:Oncogene Proteins; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D008024:Ligands; C498001:NCOA2 protein, human; C111382:NCOA4 protein, human; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D056918:Nuclear Receptor Coactivators; D000078723:Nuclear Receptor Interacting Protein 1; D015513:Oncogene Proteins; D011944:Receptors, Androgen; D015534:Trans-Activators; D014157:Transcription Factors; D005973:Glutamine; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D007930:Leucine