Mechanisms of Hippo pathway regulation.
Mechanisms of Hippo pathway regulation.
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DOI：
10.1101/gad.274027.115
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发表时间：
2016-01-01
影响因子：
10.5
通讯作者：
Guan KL
中科院分区：
文献类型：
--
作者：
Meng Z;Moroishi T;Guan KL
在这篇综述中，孟等人聚焦于我们对核心Hippo激酶级联分子作用理解的最新进展，并讨论了Hippo通路调控和功能方面的关键未解决问题。
Hippo通路最初是在20年前对黑腹果蝇组织生长的筛选中被发现的，并且在过去几年中在果蝇和哺乳动物中都得到了广泛研究。Hippo通路的核心由一个激酶级联、转录共激活因子和DNA结合伙伴组成。近期研究已将Hippo通路扩展为一个包含30多个组分的复杂信号网络。该通路受细胞内在机制调控，例如细胞 - 细胞接触、细胞极性和肌动蛋白细胞骨架，以及多种信号，包括细胞能量状态、机械信号和通过G蛋白偶联受体起作用的激素信号。Hippo通路的主要功能已被确定为限制成年个体的组织生长以及调节发育器官中的细胞增殖、分化和迁移。此外，Hippo通路的失调会导致异常的细胞生长和肿瘤形成。在这篇综述中，我们聚焦于我们对核心Hippo激酶级联分子作用理解的最新进展，并讨论Hippo通路调控和功能方面的关键未解决问题。
In this review, Meng et al. focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in Hippo pathway regulation and function. The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.