Phosphorylation regulation of SRp38 by cell signaling

描述(由申请人提供)： 前信使核糖核酸剪接是真核基因表达中不可或缺的一步。剪接对细胞的生存、增殖、发育具有重要的调控作用，剪接缺陷与许多遗传性疾病有关。虽然剪接的基本机制已经被很好地描述，但关于剪接是如何由细胞信号调控的还知之甚少。SRp38是一种通用的剪接抑制因子，在有丝分裂和热休克等细胞应激反应中被去磷酸化激活。本研究旨在通过细胞周期和应激信号通路来研究SRp38的磷酸化调控。这项研究的结果不仅将揭示磷酸酶在调节SR蛋白活性中的作用，而且还将启发我们了解细胞信号调节剪接的一般机制。

DESCRIPTION (provided by applicant): Pre-mRNA splicing is an integral step of eukaryotic gene expression. Splicing its regulation is important for cell survival, proliferation, development, and defects in splicing are associated with many genetic diseases. Although the basic mechanisms of splicing have been well characterized, little is known about how splicing is regulated by cell signaling. SRp38 is a general splicing repressor that is activated by dephosphorylation specifically in mitosis, and in response to heat shock and other cellular stress. This proposed study is to investigate the phosphorylation regulation of SRp38 by the cell cycle and the stress signaling pathways. Results of this study will not only reveal the role of phosphatases in regulating SR protein activity, but also enlighten us as to the general mechanisms by which cell signaling regulates splicing.