Department of Molecular Cell Biology, The Weizmann Institute, Rehovot, Israel.
Cell Death Differ. 2018 Jan;25(1):81-92. doi: 10.1038/cdd.2017.163. Epub 2017 Oct 6.
The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ. A wealth of accumulated data suggests a complex and delicate regulatory network connecting the p53 and Hippo pathways, in a highly context-specific manner. This generates multiple layers of interaction, ranging from interdependent and collaborative signaling to apparent antagonistic activity. Furthermore, genetic and epigenetic alterations can disrupt this homeostatic network, paving the way to genomic instability and cancer. This strengthens the need to better understand the nuances that control the molecular function of each component and the cross-talk between the different components. Here, we review interactions between the p53 and Hippo pathways within a subset of physiological contexts, focusing on normal stem cells and development, as well as regulation of apoptosis, senescence and metabolism in transformed cells.
p53 家族的三个成员，p53、p63 和 p73，在结构上相似，并具有许多生化活性。然而，除了它们在保护基因组保真度方面的共同基本作用外，每个成员都获得了与不同的细胞自主和非自主过程相关的独特功能。与 p53 家族类似，Hippo 信号通路影响多种细胞过程，从细胞周期和代谢到发育和肿瘤抑制。核心 Hippo 模块由抑癌 MST-LATS 激酶和致癌转录共效应因子 YAP 和 TAZ 组成。大量积累的数据表明，p53 和 Hippo 通路之间存在一个复杂而微妙的调节网络，具有高度的特定上下文方式。这产生了多层次的相互作用，从相互依赖和协作的信号到明显的拮抗活性。此外，遗传和表观遗传改变可以破坏这个平衡网络，为基因组不稳定性和癌症铺平道路。这就加强了需要更好地理解控制每个组成部分的分子功能以及不同组成部分之间的相互作用的细微差别。在这里，我们在一组生理环境中回顾了 p53 和 Hippo 通路之间的相互作用，重点关注正常干细胞和发育，以及转化细胞中细胞凋亡、衰老和代谢的调节。
