title: Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH(2)-terminal domain.
abstract: Activation function 2 in the ligand binding domain of nuclear receptors forms a hydrophobic cleft that binds the LXXLL motif of p160 transcriptional coactivators. Here we provide evidence that activation function 2 in the androgen receptor serves as the contact site for the androgen dependent NH(2)- and carboxyl-terminal interaction of the androgen receptor and only weakly interacts with p160 coactivators in an LXXLL-dependent manner. Mutagenesis studies indicate that it is the NH(2)-/carboxyl-terminal interaction that is required by activation function 2 to stabilize helix 12 and slow androgen dissociation critical for androgen receptor activity in vivo. The androgen receptor recruits p160 coactivators through its NH(2)-terminal and DNA binding domains in an LXXLL motif-independent manner. The results suggest a novel function for activation function 2 and a unique mechanism of nuclear receptor transactivation.
authors.affiliation: Laboratories for Reproductive Biology, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599-7500, USA.
authors.forename: B
authors.initials: B
authors.lastname: He
authors.forename: J A
authors.initials: JA
authors.lastname: Kemppainen
authors.forename: J J
authors.initials: JJ
authors.lastname: Voegel
authors.forename: H
authors.initials: H
authors.lastname: Gronemeyer
authors.forename: E M
authors.initials: EM
authors.lastname: Wilson
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D006801:Humans; D017433:Protein Structure, Secondary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
chemical_list: D011944:Receptors, Androgen