Retrieved April 15, 2024, from https://hstalks.com/bs/491/.
Introduction Mechanisms of androgen action Androgen receptor (1) Testosterone and dihydrotestosterone bind AR Phenotypic effect of mutation in AR receptor Mutations in the androgen receptor AR transcriptional activity and DHT/ testosterone Testosterone dissociates faster than DHT [3H]R1881 dissociation from AR, AR507-920 Androgen receptor N/C interaction Androgen receptor (2) A model of the FXXLF motif Charge polarity of FXXLF motifs binding AR AR ligand binding domain AR20-30 RGAFQNLFQSV bound to AF2 in AR AR FXXLF motif Androgen-induced N/C interaction Requirement for AR N/C interaction and TIF2 Androgen dependent stabilization of AR AR N/C interaction The interaction of the motifs with the AR LBD AR FXXLF - SRC/p160 LXXLL competition SRC/p160 - nuclear receptor coactivators family LXXLL motif forms amphipathic alpha-helix Superimposed TIF2 LXXLL and AR FXXLF N/C interaction represses TIF2 recruitment Recruitment of nuclear receptor coregulators Melanoma antigen gene protein-11 (MAGE-11) Some of the features of MAGE-11 Human MAGE-11 Mammalian two hybrid interaction assay AR NH2-terminal FXXLF motif fragments FXXLF dependent AR - MAGE-11 interaction Overlapping AR FXXLF binding sites MAGE-11 specifically binds the AR FXXLF motif Colocalization of AR and MAGE-11 in COS cells Increased AR transactivation of PSA-Luc AR-AF2 activation by SRC/p160 coactivators AF1 and AF2 active in reproductive tract tissues Androgen insensitivity syndrome Phenotypic grades of androgen insensitivity AR-R1881-FXXLF Dissociation of [3H]R1881 AR AIS mutations disrupt F27 binding to AF2 AR AIS mutations disrupt F23 binding to AF2 AR AIS mutation in ligand gateway Prostate cancer AR in BPH and recurrent prostate cancer (CaP) Mechanisms of prostate cancer progression Increased SRC/p160 coactivator levels in CaP Highly expressed cofactors in prostate cancer AR mutations in CaP increase AR activity Three gain-of-function AR mutations in CaP Summary