Masuhiro Yoshikazu, Mezaki Yoshihiro, Sakari Matomo, Takeyama Ken-ichi, Yoshida Tasuku, Inoue Kunio, Yanagisawa Junn, Hanazawa Shigemasa, O'malley Bert W, Kato Shigeaki
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8126-31. doi: 10.1073/pnas.0503197102. Epub 2005 May 26.
Mitogen-activated protein kinase-mediated growth factor signals are known to augment the ligand-induced transactivation function of nuclear estrogen receptor alpha (ERalpha) through phosphorylation of Ser-118 within the ERalpha N-terminal transactivation (activation function-1) domain. We identified the spliceosome component splicing factor (SF)3a p120 as a coactivator specific for human ERalpha (hERalpha) activation function-1 that physically associated with ERalpha dependent on the phosphorylation state of Ser-118. SF3a p120 potentiated hERalpha-mediated RNA splicing, and notably, the potentiation of RNA splicing by SF3a p120 depended on hER Ser-118 phosphorylation. Thus, our findings suggest a mechanism by which growth factor signaling can regulate gene expression through the modulation of RNA splicing efficiency via phosphorylation of sequence-specific activators, after association between such activators and the spliceosome.
已知丝裂原活化蛋白激酶介导的生长因子信号通过雌激素受体α（ERα）N端反式激活（激活功能-1）结构域内Ser-118的磷酸化增强配体诱导的核雌激素受体α（ERα）的反式激活功能。我们鉴定出剪接体成分剪接因子（SF）3a p120是一种对人ERα（hERα）激活功能-1具有特异性的共激活因子，它根据Ser-118的磷酸化状态与ERα发生物理关联。SF3a p120增强了hERα介导的RNA剪接，值得注意的是，SF3a p120对RNA剪接的增强作用取决于hER Ser-118的磷酸化。因此，我们的研究结果提示了一种机制，即生长因子信号传导可通过在序列特异性激活因子与剪接体结合后，经由对这些激活因子的磷酸化来调节RNA剪接效率，从而调控基因表达。
