Hippo-Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior.,WIREs Mechanisms of Disease

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Hippo-Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior.
WIREs Mechanisms of Disease ( IF 4.6 ) Pub Date : 2019-12-11 , DOI: 10.1002/wdev.371
Benjamin J van Soldt _{1,

2} , Wellington V Cardoso _{1,

2}

Affiliation

The Hippo pathway has emerged as a crucial integrator of signals in biological events from development to adulthood and in diseases. Although extensively studied in Drosophila and in cell cultures, major gaps of knowledge still remain on how this pathway functions in mammalian systems. The pathway consists of a growing number of components, including core kinases and adaptor proteins, which control the subcellular localization of the transcriptional co‐activators Yap and Taz through phosphorylation of serines at key sites. When localized to the nucleus, Yap/Taz interact with TEAD transcription factors to induce transcriptional programs of proliferation, stemness, and growth. In the cytoplasm, Yap/Taz interact with multiple pathways to regulate a variety of cellular functions or are targeted for degradation. The Hippo pathway receives cues from diverse intracellular and extracellular inputs, including growth factor and integrin signaling, polarity complexes, and cell–cell junctions. This review highlights the mechanisms of regulation of Yap/Taz nucleocytoplasmic shuttling and their implications for epithelial cell behavior using the lung as an intriguing example of this paradigm.

中文翻译：

Hippo-Yap/Taz 信号：复杂的网络相互作用和对上皮细胞行为的影响。

Hippo 通路已成为从发育到成年的生物事件和疾病中信号的关键整合器。尽管在果蝇中进行了广泛研究在细胞培养中，关于该通路如何在哺乳动物系统中发挥作用的知识仍然存在重大差距。该通路由越来越多的成分组成，包括核心激酶和衔接蛋白，它们通过关键位点的丝氨酸磷酸化来控制转录共激活因子 Yap 和 Taz 的亚细胞定位。当定位于细胞核时，Yap/Taz 与 TEAD 转录因子相互作用以诱导增殖、干性和生长的转录程序。在细胞质中，Yap/Taz 与多种途径相互作用以调节多种细胞功能或靶向降解。Hippo 通路接收来自不同细胞内和细胞外输入的信号，包括生长因子和整合素信号、极性复合物和细胞-细胞连接。

更新日期：2019-12-11

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