Mechanism of androgen receptor corepression by CKßBP2/CRIF1, a multifunctional transcription factor coregulator expressed in prostate cancer.
Mol Cell Endocrinol
; 382(1): 302-313, 2014 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-24103312
ABSTRACT
The transcription factor coregulator Casein kinase IIß-binding protein 2 or CR6-interacting factor 1 (CKßBP2/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 CKßBP2/CRIF1 localization in chromatin is determined by AR. In this study we show also that CKßBP2/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 CKßBP2/CRIF1 interferes with AR activation functions 1 and 2. CKßBP2/CRIF1 is expressed mainly in stromal cells of benign prostatic hyperplasia and in stroma and epithelium of prostate cancer. CKßBP2/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 CKßBP2/CRIF1 is a STAT3 interacting protein and reported to be a coactivator of STAT3. CKßBP2/CRIF1 is expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR repressor effect of CKßBP2/CRIF1 and allow AR regulation of prostate cancer growth.
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MEDLINE
Assunto principal:
Neoplasias da Próstata
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Proteínas Nucleares
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Receptores Androgênicos
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Proteínas de Ciclo Celular
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Proteínas Correpressoras
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article