课题基金基金详情
磷酸戊糖途径调节Aurora-A激酶活性及分裂进程的机制研究
结题报告
批准号:
32000528
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
程傲星
依托单位:
学科分类:
细胞代谢、应激及稳态调控
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
程傲星
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中文摘要
除了参与中心体成熟和两极纺锤体形成,细胞周期调控激酶Aurora-A在多种肿瘤中过表达,促进肿瘤恶性进展。研究发现促癌基因广泛参与肿瘤代谢重编程的调控,但Aurora-A和肿瘤代谢的关系还知之甚少。我们前期研究发现Aurora-A可以通过磷酸化乳酸脱氢酶B,增强糖酵解和生物合成,促进肿瘤细胞S-G2期进程(Nat.Comm.2019)。近期,我们还发现一个代谢支路,磷酸戊糖途径可以调节分裂期Aurora-A的活性,且其代谢产物NADPH和Aurora-A能发生直接的相互作用,暗示磷酸戊糖途径可能通过NADPH调节分裂期Aurora-A的活性。因此,在本课题中我们计划深入研究NADPH和分裂期Aurora-A活性的关系,进而揭示磷酸戊糖途径及其代谢物NADPH在细胞分裂和肿瘤进展中新的调控机制。本研究有助于深入理解肿瘤代谢状态对于分裂进程及染色体精准分离的重要意义,可为肿瘤的诊疗提供新思路。
英文摘要
In addition to participating in centrosome maturation and bipolar spindle formation, the cell cycle-regulated kinase Aurora-A is overexpressed in a variety of tumors and can promote tumorigenesis and tumor progression. It is reported that oncogenes are widely involved in the regulation of tumor metabolism reprogramming. However, little is known about the relationship between Aurora-A and tumor metabolism. Our previous studies found that Aurora-A can promote glycolysis, bio-synthesis and S-G2 progression by phosphorylation of LDHB(Nat.Comm.2019). Recently, we also found that a branch of sugar metabolism, the pentose phosphate pathway can specifically regulate the kinase activity of Aurora-A in mitosis, and its metabolite NADPH can bind to Aurora-A directly, indicating that the pentose phosphate pathway may regulate the activity and function of Aurora-A through NADPH. Therefore, in this project, we plan to study the relationship between NADPH and the activity of Aurora-A kinase in cell division, and reveal the new functions of the pentose phosphate pathway and its metabolite NADPH in the regulation of cell division and tumor progression. This study is helpful for understanding the significance of cell metabolism for timely and accurate segregation of chromosomes, and can provide new ideas for the diagnosis and treatment of tumors.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1016/j.jbc.2022.102561
发表时间:2022-11
期刊:JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子:4.8
作者:Jiang, Ya;Wang, Ting;Sheng, Dandan;Han, Chaoqiang;Xu, Tian;Zhang, Peng;You, Weiyi;Fan, Weiwei;Zhang, Zhiyong;Jin, Tengchuan;Duan, Xiaotao;Yuan, Xiao;Liu, Xing;Zhang, Kaiguang;Ruan, Ke;Shi, Jue;Guo, Jing;Cheng, Aoxing;Yang, Zhenye
通讯作者:Yang, Zhenye
Development of a one-plasmid system to replace the endogenous protein with point mutation for post-translational modification studies
开发一种单质粒系统,用点突变替代内源蛋白,用于翻译后修饰研究
DOI:10.1007/s11033-021-06693-3
发表时间:2021-11-11
期刊:MOLECULAR BIOLOGY REPORTS
影响因子:2.8
作者:Ishrat, Iqra;Cheng, Aoxing;Yang, Zhenye
通讯作者:Yang, Zhenye
Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells
能量限制导致癌细胞中期延迟和染色体错误分离
DOI:10.1080/15384101.2021.1930679
发表时间:2021-05
期刊:Cell Cycle
影响因子:4.3
作者:Cheng Aoxing;Jiang Ya;Wang Ting;Yu Fazhi;Ishrat Iqra;Zhang Dongming;Ji Xiaoyang;Chen Minhua;Xiao Weihua;Li Qing;Zhang Kaiguang;Niu Gang;Shi Jue;Pan Yueyin;Yang Zhenye;Guo Jing
通讯作者:Guo Jing
DOI:doi: 10.1038/s42255-023-00832-9
发表时间:2023
期刊:Nature Metabolism
影响因子:20.8
作者:Aoxing Cheng;Tian Xu;Weiyi You;Ting Wang;Dongming Zhang;Huimin Guo;Haiyan Zhang;Xin Pan;Yucai Wang;Liu Liu;Kaiguang Zhang;Jue Shi;Xuebiao Yao;Jing Guo;Zhenye Yang
通讯作者:Zhenye Yang
国内基金
海外基金