Phosphorylation regulation of SRp38 by cell signaling

描述（由申请人提供）： 前体mRNA剪接是真核基因表达的一个重要步骤。其剪接调控对细胞存活、增殖、发育非常重要，剪接缺陷与许多遗传疾病有关。 虽然剪接的基本机制已经得到很好的表征，但对剪接如何受细胞信号转导的调节知之甚少。SRp38是一种通用的剪接阻遏物，在有丝分裂中特异性地通过去磷酸化激活，并且响应于热休克和其他细胞应激。本研究旨在探讨细胞周期和应激信号通路对SRp38磷酸化的调控。本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.