MEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer
MEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer
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MEK1 促进 YAP 且它们的相互作用对于肝癌的肿瘤发生至关重要
DOI：
10.1016/j.febslet.2013.10.042
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发表时间：
2013-12-11
期刊：
影响因子：
3.5
通讯作者：
Sun, Fenyong
中科院分区：
文献类型：
--
作者：
Li, Lanlan;Wang, Jiayi;Sun, Fenyong
丝裂原活化蛋白激酶激酶1 （MAP2K1/MEK1）和yes相关蛋白（YAP）是Hippo信号通路的下游效应物，与肝癌的发生有关。然而，对于MEK1是否以及如何与YAP相互作用知之甚少。在这项研究中，我们发现MEK1-YAP相互作用在体外和体内对肝癌细胞增殖和转化表型的维持至关重要。此外，MEK1和YAP蛋白在人类肝癌样本中密切相关。从机制上讲，PD98059和U0126以及RNAi对MEK1的抑制可减少含有E3泛素蛋白连接酶（BTRC）的β -转导重复序列，而BTRC是潜在的内源性YAP保护因子。结构化的总结蛋白质相互作用:YAP身体与MEK1通过反标记coimmunoprecipitation(查看交互)BTRC和MEK1 colocalize通过荧光显微镜(查看交互)YAP身体与MEK1由抗诱饵coimmunoprecipitation(查看交互)MEK1身体与BTRC的反标签coimmunoprecipitation(查看交互)BTRC身体与MEK1由抗诱饵coimmunoprecipitation(查看交互)MEK1和YAP colocalize荧光显微镜（观察相互作用）(C) 2013年欧洲生化学会联合会。Elsevier B.V.版权所有。
Mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1) as well as Yes-associated protein (YAP), the downstream effector of Hippo signaling pathway, is linked to hepatocarcinogenesis. However, little is known about whether and how MEK1 interacts with YAP. In this study, we find that MEK1-YAP interaction is critical for liver cancer cell proliferation and maintenance of transformed phenotypes both in vitro and in vivo. Moreover, MEK1 and YAP proteins are closely correlated in human liver cancer samples. Mechanistically, inhibition of MEK1 by both PD98059 and U0126 as well as RNAi reduces beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), which acts as a potential endogenous YAP protector.Structured summary of protein interactions:YAP physically interacts with MEK1 by anti tag coimmunoprecipitation (View interaction)BTRC and MEK1 colocalize by fluorescence microscopy (View interaction)YAP physically interacts with MEK1 by anti bait coimmunoprecipitation (View interaction)MEK1 physically interacts with BTRC by anti tag coimmunoprecipitation (View interaction)BTRC physically interacts with MEK1 by anti bait coimmunoprecipitation (View interaction)MEK1 and YAP colocalize by fluorescence microscopy (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.