CACUL1 functions as a negative regulator of androgen receptor in prostate cancer cells.
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.
Mesh Terms:
Androgen Antagonists, Anilides, Antineoplastic Agents, Hormonal, Cell Line, Tumor, Cullin Proteins, Gene Expression Regulation, Neoplastic, Histone Demethylases, Histones, Humans, Male, Methylation, Nitriles, Promoter Regions, Genetic, Prostatic Neoplasms, Castration-Resistant, Protein Binding, RNA Interference, Receptors, Androgen, Signal Transduction, Tosyl Compounds, Transcription, Genetic, Transfection
Androgen Antagonists, Anilides, Antineoplastic Agents, Hormonal, Cell Line, Tumor, Cullin Proteins, Gene Expression Regulation, Neoplastic, Histone Demethylases, Histones, Humans, Male, Methylation, Nitriles, Promoter Regions, Genetic, Prostatic Neoplasms, Castration-Resistant, Protein Binding, RNA Interference, Receptors, Androgen, Signal Transduction, Tosyl Compounds, Transcription, Genetic, Transfection
Cancer Lett.
Date: Dec. 01, 2015
PubMed ID: 27085459
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