title: CACUL1 functions as a negative regulator of androgen receptor in prostate cancer cells.
abstract: The androgen receptor (AR) plays a critical role in the initiation and progression of prostate cancer (PCa), and thus its regulation is an important tool in PCa therapy. Here, we report that CDK2-associated cullin 1 (CACUL1) directly associates with AR and suppresses AR transcriptional activity. In addition, CACUL1 represses histone demethylase LSD1-mediated AR transactivation by competing with LSD1 for AR binding. Depletion of CACUL1 enhances the LSD1 occupancy of the AR-target promoter, accompanied by decreased accumulation of H3K9me2, a repressive transcriptional marker. CACUL1 and LSD1 oppositely regulate CDX-induced cell death in AR-positive LNCaP and metastatic castrate-resistant LNCaP-LN3 cells. These data suggest that CACUL1 impairs LSD1-mediated activation of AR, thereby implicating it as a potential antitumor target in PCa.
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Hanbyeul
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Sang Hyup
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology/Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea. Electronic address: nbrejk@dankook.ac.kr.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008745:Methylation; D009570:Nitriles / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014105:Tosyl Compounds / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; C546534:CACUL1 protein, human; D044842:Cullin Proteins; D006657:Histones; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: AR; CACUL1; LSD1; Prostate cancer; Transcriptional activity