TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells

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• 作者：Misato Kikuchi ; Fumihiko Okumura ; Tadasuke Tsukiyama ; Masashi Watanabe ; Naoto Miyajima ; Junji Tanaka ; Masahiro Imamura ; Shigetsugu Hatakeyama
• 关键词：TRIM24 ; Androgen receptor ; Prostate cancer ; BRD7
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：1793
• 期：12
• 页码：1828-1836
• 全文大小：612 K

文摘

The androgen receptor (AR) is a ligand-dependent transcription factor that belongs to the family of nuclear receptors, and its activity is regulated by numerous AR coregulators. AR plays an important role in prostate development and cancer. In this study, we found that TRIM24/transcriptional intermediary factor 1α (TIF1α), which is known as a ligand-dependent nuclear receptor co-regulator, interacts with AR and enhances transcriptional activity of AR by dihydrotestosterone in prostate cancer cells. We showed that TRIM24 functionally interacts with TIP60, which acts as a coactivator of AR and synergizes with TIP60 in the transactivation of AR. We also showed that TRIM24 binds to bromodomain containing 7 (BRD7), which can negatively regulate cell proliferation and growth. A luciferase assay indicated that BRD7 represses the AR transactivation activity upregulated by TRIM24. These findings indicate that TRIM24 regulates AR-mediated transcription in collaboration with TIP60 and BRD7.