Hippo信号通路结构生物学研究进展

doi:10.16288/j.yczz.17-062

遗传 ›› 2017, Vol. 39 ›› Issue (7): 659-674.doi: 10.16288/j.yczz.17-062

Hippo信号通路结构生物学研究进展

胡立桥¹(),周兆才²,田伟¹()

1. 华中科技大学生命科学与技术学院,武汉 430074
2. 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,上海 200031

收稿日期:2017-02-23 修回日期:2017-03-15 出版日期:2017-07-20 发布日期:2017-07-04
作者简介:胡立桥,博士研究生,研究方向：结构生物学。E-mail: liq@hust.edu.cn|田伟，博士，教授，研究方向：生物化学和结构生物学。E-mail: tianwei@hust.edu.cn
基金资助:
国家自然科学基金项目(编号：31500629)资助[Supported by the National Natural Science Foundation of China (No. 31500629)]

Research progresses on the molecular structure of the Hippo signaling pathway components

Liqiao Hu¹(),Zhaocai Zhou²,Wei Tian¹()

1. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
2. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Received:2017-02-23 Revised:2017-03-15 Online:2017-07-20 Published:2017-07-04

摘要/Abstract

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。

关键词: Hippo信号通路, 癌症, 蛋白质相互作用, 蛋白质分子结构, 抑制剂

Abstract:

The Hippo signaling pathway has been identified to be involved in development and tissue homeostasis during the past decade, and is evolutionarily conserved from Drosophila to mammals. It transduces the signal through a series of protein-protein interaction and kinase cascades, to control the cell number and organ size by inhibiting cell proliferation and promoting apoptosis. Dysregulation of the Hippo signaling pathway is associated with tumorigenesis and cancers, so it is a crucial target for cancer therapy and regeneration medicine. Most of the Hippo signaling pathway components have been identified, and the cellular function and molecular mechanism have been revealed by structural and functional researches. In this review, we summarize the molecular structure of Hippo signaling pathway components and related targeting inhibitors from a structural view. We hope to improve the understandings of the regulation mechanism of the Hippo signaling transduction, and facilitate further functional studies and potential therapeutic interventions.

Key words: Hippo signaling pathway, cancer, protein-protein interaction, molecular structure of protein, inhibitor

胡立桥,周兆才,田伟. Hippo信号通路结构生物学研究进展[J]. 遗传, 2017, 39(7): 659-674.

Liqiao Hu,Zhaocai Zhou,Wei Tian. Research progresses on the molecular structure of the Hippo signaling pathway components[J]. Hereditas(Beijing), 2017, 39(7): 659-674.

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Research progresses on the molecular structure of the Hippo signaling pathway components

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