线性泛素化E3酶复合体LUBAC调控初级纤毛的功能与机制研究
结题报告
批准号:
82002970
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
吴敏
学科分类:
肿瘤发生
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
吴敏
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中文摘要
初级纤毛存在于大多数动物细胞表面,细胞可通过初级纤毛感知外界信号的变化,且初级纤毛可协助外界信号转导至细胞内从而产生相应的细胞应答。初级纤毛发生缺陷会引起一系列疾病,从发育缺陷到肥胖症、糖尿病甚至肿瘤。线性泛素化E3酶LUBAC是已知的唯一一个介导底物发生线性泛素化修饰的E3酶,目前研究显示它主要在先天免疫中发挥关键调控作用,关于它的其他功能尚知之甚少。课题组前期研究揭示了LUBAC的新功能—调控细胞有丝分裂进程,维持基因组的稳定性(Nat. Commun., 2019,第一作者)。近期结果提示,LUBAC通过特异调控开关分子CP110促进初级纤毛的发生。在此基础上,本项目拟从分子、细胞、动物及临床水平深入探索LUBAC对初级纤毛发生的调控作用,及其对胚胎发育、肿瘤发生的影响。以上研究将可能进一步阐明纤毛组装的分子机制,同时也为纤毛缺陷性疾病及肿瘤的早期诊断和药物治疗提供新的干预靶点。
英文摘要
The primary cilia are present in most types of animal cells. Cells can receive extracellular signals through the primary cilia, and the cilia can assist in transferring signals into cells, followed by cellular responses. Defects in ciliogenesis can cause a range of diseases, from developmental defects to obesity, diabetes and even tumors. The linear ubiquitin ligase complex LUBAC is the only known E3 ligase that conjugates linear ubiquitin chains to substrates. It is well known to play an important role in innate immune, but other functions are largely unknown. Our previous study revealed a new function of LUBAC, which can regulate mitosis and maintain genomic stability (Nat. Commun., 2019, first author). Recently, we found that LUBAC promotes ciliogenesis by specifically regulating the destruction of key factor CP110. Based on these findings, we are trying to evaluate the effect of LUBAC on ciliogenesis thoroughly in the molecular, cellular, animal, and clinical level, and explore its role in embryonic development and tumorigenesis. Our study may shed a new light on the regulatory mechanism of ciliogenesis, and would provide new early diagnosis and therapy targets for ciliopathies and 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
Rhythmic cilia changes support SCN neuron coherence in circadian clock
有节律的纤毛变化支持昼夜节律时钟中的 SCN 神经元一致性
DOI:10.1126/science.abm1962
发表时间:2023
期刊:Science
影响因子:56.9
作者:Hai;Sen Li;Yu;Yu;Pei;Li;Guang;Xiao;Min Wu;Zeng;Tingting Li;Huaibin Hu;Jin;Xiao;Jia;Qiu;Kai Wang;Tao Zhang;Tao Zhou;Ai;Xue;Hui
通讯作者:Hui
DOI:10.1038/s41467-021-20986-y
发表时间:2021-01-28
期刊:Nature communications
影响因子:16.6
作者:Hu HB;Song ZQ;Song GP;Li S;Tu HQ;Wu M;Zhang YC;Yuan JF;Li TT;Li PY;Xu YL;Shen XL;Han QY;Li AL;Zhou T;Chun J;Zhang XM;Li HY
通讯作者:Li HY
国内基金
海外基金