Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599-7500, USA.
J Biol Chem. 2009 Dec 11;284(50):34793-808. doi: 10.1074/jbc.M109.065979. Epub 2009 Oct 14.
Androgen-dependent transcriptional activity by the androgen receptor (AR) and its coregulators is required for male reproductive development and function. In humans and other primates, melanoma antigen gene protein-A11 (MAGE-11) is an AR selective coregulator that increases AR transcriptional activity. Here we show that the interaction between AR and MAGE-11 is mediated by AR NH(2)-terminal FXXLF motif binding to a highly conserved MAGE-11 F-box in the MAGE homology domain, and is modulated by serum stimulation of mitogen-activated protein kinase phosphorylation of MAGE-11 Ser-174. The MAGE-11-dependent increase in AR transcriptional activity is mediated by a direct interaction between MAGE-11 and transcriptional intermediary factor 2 (TIF2) through the NH(2)-terminal region of TIF2, and by a MAGE-11 FXXIF motif interaction with an F-box-like region in activation domain 1 of TIF2. The results suggest that MAGE-11 functions as a bridging factor to recruit AR coactivators through a novel FXX(L/I)F motif-F-box interaction paradigm.
雄激素受体（AR）及其共激活因子的雄激素依赖性转录活性是男性生殖发育和功能所必需的。在人类和其他灵长类动物中，黑色素瘤抗原基因蛋白 A11（MAGE-11）是一种 AR 选择性共激活因子，可增加 AR 转录活性。在这里，我们表明 AR 和 MAGE-11 之间的相互作用是通过 AR NH2-末端 FXXLF 基序与 MAGE 同源结构域中高度保守的 MAGE-11 F 框结合来介导的，并且通过丝裂原激活的蛋白激酶对 MAGE-11 Ser-174 的磷酸化来调节。MAGE-11 依赖性 AR 转录活性的增加是通过 MAGE-11 与转录中介因子 2（TIF2）的 NH2-末端区域之间的直接相互作用介导的，并且通过 MAGE-11 FXXIF 基序与 TIF2 的激活域 1 中的 F-框样区域相互作用介导的。结果表明，MAGE-11 作为桥连因子，通过一种新的 FXX（L/I）F 基序-F 框相互作用范例来募集 AR 共激活因子。
