Hippo信号通路结构生物学研究进展

发布时间：2018-07-07 23:24

本文选题：Hippo信号通路 + 癌症　；参考：《遗传》2017年07期

【摘要】：生物体内存在多种信号转导通路参与发育调控和组织稳态维持等重要过程,其信号异常与多种疾病特别是癌症的发生和发展密切相关。进化上高度保守的Hippo信号通路在个体发育和稳态平衡中发挥极为关键的作用。Hippo信号通路主要通过一系列相关激酶的相互作用和级联磷酸化来传递信号,能抑制细胞增殖并促进凋亡,在很多组织器官中控制细胞数量和器官大小。Hippo信号通路在一系列恶性肿瘤中出现显著异常,被认为是癌症治疗和再生医学的重要靶标。目前,Hippo信号通路中大部分关键组分已经确定,而其具体信号调控机制及功能正在完善之中。本文总结了目前已知的Hippo信号通路各蛋白成员的结构信息,重点从结构生物学角度对其信号的转导与调控机制进行分析,并对已有的Hippo信号通路靶向小分子及多肽抑制剂进行梳理,以期深化人们对该通路关键蛋白质机器的理解,并进一步促进相关的功能研究和潜在的治疗干预研发。
[Abstract]:There are many signal transduction pathways involved in the regulation of development and the maintenance of tissue homeostasis. Their signal abnormalities are closely related to the occurrence and development of many diseases, especially cancer. The highly conserved Hippo signaling pathway plays a crucial role in ontogeny and homeostasis. The Hippo signaling pathway transmits signals through a series of related kinase interactions and cascade phosphorylation. It can inhibit cell proliferation and promote apoptosis. In many tissues and organs, the number of cells and organ size. Hippo signaling pathway is significantly abnormal in a series of malignant tumors, which is considered to be an important target of cancer therapy and regenerative medicine. At present, most of the key components in Hippo signal pathway have been identified, and its specific signal regulation mechanism and function are being improved. In this paper, the structural information of the members of the Hippo signaling pathway is summarized, and the mechanism of its signal transduction and regulation is analyzed from the point of view of structural biology. And the existing Hippo signaling pathway targeting small molecules and polypeptide inhibitors were combed in order to deepen the understanding of the key protein machinery of the pathway and to further promote the related functional research and potential therapeutic intervention research.
【作者单位】：华中科技大学生命科学与技术学院;中国科学院上海生命科学研究院生物化学与细胞生物学研究所;
【基金】：国家自然科学基金项目(编号:31500629)资助~~
【分类号】：R730.2

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