Kikuchi Misato, Okumura Fumihiko, Tsukiyama Tadasuke, Watanabe Masashi, Miyajima Naoto, Tanaka Junji, Imamura Masahiro, Hatakeyama Shigetsugu
Department of Biochemistry, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Biochim Biophys Acta. 2009 Dec;1793(12):1828-36. doi: 10.1016/j.bbamcr.2009.11.001. Epub 2009 Nov 10.
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 1alpha (TIF1alpha), 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.
雄激素受体（AR）是一种依赖配体的转录因子，属于核受体家族，其活性受众多AR共调节因子调控。AR在前列腺发育和癌症中发挥重要作用。在本研究中，我们发现TRIM24/转录中间因子1α（TIF1α），即一种已知的依赖配体的核受体共调节因子，在前列腺癌细胞中与AR相互作用，并通过双氢睾酮增强AR的转录活性。我们表明TRIM24在功能上与TIP60相互作用，TIP60作为AR的共激活因子，并在AR的反式激活中与TIP60协同作用。我们还表明TRIM24与含溴结构域7（BRD7）结合，BRD7可负向调节细胞增殖和生长。荧光素酶测定表明BRD7抑制由TRIM24上调的AR反式激活活性。这些发现表明TRIM24与TIP60和BRD7协同调节AR介导的转录。
