CDK11需要一個關鍵的激活子SAP30BP來調節pre-mRNA剪接

2023年12月，中國科學院分子細胞科學**研究中心；中國科學院上海生物化學與細胞生物學研究所；中國科學院RNA科學與工程重點實驗室；武漢大學生命科學學院；太康生命與醫學科學中心；RNA研究所；湖北省細胞穩態重點實驗室；中國科學院分析化學分離科學重點實驗室；武漢中國科學院大連化學物理研究所國家色譜研究中心；中國科學院大學杭州高等研究院生命科學學院浙江省系統健康科學重點實驗室(Key Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China；College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, China；CAS Key Laboratory of Separation Sciences for Analytical Chemistry,   National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China；Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences,Hangzhou, China) Jing Fan老師研究團隊在《The EMBO Journal》上發表論文：

“CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing”

“CDK11需要一個關鍵的激活子SAP30BP來調節pre-mRNA剪接”

Abstract：

CDK11 is an emerging druggable target for cancer therapy due to its prevalent roles in phosphorylating critical transcription and splicing factors and in facilitating cell cycle progression in cancer cells. Like other cyclin-dependent kinases, CDK11 requires its cognate cyclin, cyclin L1 or cyclin L2, for activation. However, little is known about how CDK11 activities might be modulated by other regulators. In this study, we show that CDK11 forms a tight complex with cyclins L1/L2 and SAP30BP, the latter of which is a poorly characterized factor. Acute degradation of SAP30BP mirrors that of CDK11 in causing widespread and strong defects in pre-mRNA splicing. Furthermore, we demonstrate that SAP30BP facilitates CDK11 kinase activities in vitro and in vivo, through ensuring the stabilities and the assembly of cyclins L1/L2 with CDK11. Together, these findings uncover SAP30BP as a critical CDK11 activator that regulates global pre-mRNA splicing.

摘要：

CDK11是一個新興的癌癥治療藥物靶點，因為它在磷酸化關鍵轉錄和剪接因子以及促進癌細胞細胞周期進程中發揮著普遍作用。像其他細胞周期蛋白依賴性激酶一樣，CDK11需要其同源細胞周期蛋白，細胞周期蛋白L1或細胞周期蛋白L2來激活。然而，對于CDK11的活性如何被其他調節因子調節，研究人員所知甚少。在這項研究中，研究人員發現CDK11與細胞周期蛋白L1/L2和SAP30BP形成緊密復合物，后者是一個特征不明顯的因子。SAP30BP的急性降解與CDK11一樣，在pre-mRNA剪接中引起廣泛而強烈的缺陷。此外，研究人員證明SAP30BP通過確保細胞周期蛋白L1/L2與CDK11的穩定性和組裝，促進了CDK11激酶在體外和體內的活性。綜上所述，這些發現揭示了SAP30BP作為一個關鍵的CDK11激活因子，調控全局pre-mRNA剪接。

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