MEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer

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.