Mai Sanyue, Qu Xiuhua, Li Ping, Ma Qingjun, Liu Xuan, Cao Cheng
Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
General Navy Hospital of PLA, 6 Fucheng Rd, Haidian District, Beijing 100037, China.
Biochem Biophys Res Commun. 2016 Apr 22;473(1):355-360. doi: 10.1016/j.bbrc.2016.03.108. Epub 2016 Mar 24.
RBM39, also known as splicing factor HCC1.4, acts as a transcriptional coactivator for the steroid nuclear receptors JUN/AP-1, ESR1/ER-α and ESR2/ER-β. RBM39 is involved in the regulation of the transcriptional responses of these steroid nuclear receptors and promotes transcriptional initiation. In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner. The results suggest that mammalian c-Abl plays an important role in steroid hormone receptor-mediated transcription by regulating RBM39.
RBM39，也被称为剪接因子HCC1.4，作为类固醇核受体JUN/AP-1、ESR1/ER-α和ESR2/ER-β的转录共激活因子发挥作用。RBM39参与这些类固醇核受体转录反应的调控并促进转录起始。在本文中，我们报道RBM39与非受体酪氨酸激酶c-Abl相互作用。c-Abl的Src同源（SH）2和SH3结构域均与RBM39相互作用。液相色谱串联质谱（LC/MS/MS）和突变分析表明，c-Abl磷酸化RBM39的主要酪氨酸磷酸化位点是Y95和Y99。结果显示，c-Abl以酪氨酸激酶依赖性方式增强RBM39对ERα和PRβ的转录共激活活性。这些结果表明，哺乳动物c-Abl通过调节RBM39在类固醇激素受体介导的转录中发挥重要作用。
