Mechanism of androgen receptor corepression by CK?BP2/CRIF1, a multifunctional transcription factor coregulator expressed in prostate cancer.

ABSTRACT: The transcription factor coregulator Casein kinase II?-binding protein 2 or CR6-interacting factor 1 (CK?BP2/CRIF1) binds the androgen receptor (AR) in prostate cancer cells and in response to dihydrotestosterone localizes with AR on the prostate-specific antigen gene enhancer, but does not bind DNA suggesting CK?BP2/CRIF1 localization in chromatin is determined by AR. In this study we show also that CK?BP2/CRIF1 inhibits wild-type AR and AR N-terminal transcriptional activity, binds to the AR C-terminal region, inhibits interaction of the AR N- and C-terminal domains (N/C interaction) and competes with p160 coactivator binding to the AR C-terminal domain, suggesting CK?BP2/CRIF1 interferes with AR activation functions 1 and 2. CK?BP2/CRIF1 is expressed mainly in stromal cells of benign prostatic hyperplasia and in stroma and epithelium of prostate cancer. CK?BP2/CRIF1 protein is increased in epithelium of androgen-dependent prostate cancer compared to benign prostatic hyperplasia and decreased slightly in castration recurrent epithelium compared to androgen-dependent prostate cancer. The multifunctional CK?BP2/CRIF1 is a STAT3 interacting protein and reported to be a coactivator of STAT3. CK?BP2/CRIF1 is expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR repressor effect of CK?BP2/CRIF1 and allow AR regulation of prostate cancer growth.

SUBMITTER: Tan JA 

PROVIDER: S-EPMC3880566 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other