拟南芥酪蛋白激酶AELs调控细胞分裂的功能及机制研究

细胞分裂是动植物生长发育的基础，阐明其调控机理至关重要。蛋白磷酸化是真核生物中最广泛的蛋白翻译后修饰，1型酪蛋白激酶(Casein Kinase 1，CK1)介导的磷酸化在动物中已被揭示参与细胞分裂并发挥重要的调控作用，然而CK1在植物细胞分裂中的功能和调控机制仍不清楚。本课题组前期的工作发现，拟南芥CK1成员AELs(Arabidopsis EL1-like)的三突变体莲座叶有丝分裂受抑制，细胞数目减少致使叶片小且生长缓慢；并且申请者通过磷酸化蛋白组学获得了候选底物。本项目将阐明植物中AELs介导的磷酸化调控细胞分裂的机理；此外，基于动植物CK1结构的保守性，本项目将寻找动物中的同源底物蛋白，进一步揭示该底物的磷酸化参与细胞分裂的调控机制。本项目的研究结果将填补CK1在植物中调控细胞分裂的空白，而动物中的调控机制及磷酸化位点将为肿瘤的精准诊断和治疗以及靶向药物的研制提供新思路。

Cell division is the basis of growth and development of plants and animals and it is important to elucidate its regulatory mechanism. As the most universal post-translational modification, protein phosphorylation, particularly those mediated by casein kinase1 (CK1, highly conserved in plants and mammals), play essential regulatory roles in various cellular processes including cell division in animals. However, the function and mechanism of CK1 in regulating plant cell division have not been reported. We here found that triple mutants of Arabidopsis EL1-like (AEL), a conserved plant CK1, presented the phenotype of small rosette leaves and retarded growth due to severe inhibition of cell mitosis, indicating that AELs are involved in the regulation of plant cell division. This project will carry out in-depth and systematic research on the regulatory mechanism of AELs mediated phosphorylation involved in cell division with model plant Arabidopsis thaliana, and further analyze the homologs of substrates in animals and elucidate the phosphorylation mechanism. This study will illustrate the molecular mechanism of CK1s-mediated phosphorylation in regulating cell mitosis in plants. In addition, identification of animal homologous proteins and phosphorylation sites will provide novel insights into the precise diagnosis and treatment of tumor as well as the development of targeted drugs.