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

• MEK1 controls both YAP expression and activity independent of ERK and Hippo pathway.
• MEK1 regulates YAP independent of transcription.
• MEK1 interacts and correlates with YAP expression in liver cancers.
• MEK1 controls BTRC expression, which may serve as a novel YAP protector.
• The interaction between YAP and MEK1 promotes 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 interactionsYAPphysically interacts with MEK1 by anti tag coimmunoprecipitation (View interaction)BTRC and MEK1colocalize by fluorescence microscopy (View interaction)YAPphysically interacts with MEK1 by anti bait coimmunoprecipitation (View interaction)MEK1physically interacts with BTRC by anti tag coimmunoprecipitation (View interaction)BTRCphysically interacts with MEK1 by anti bait coimmunoprecipitation (View interaction)MEK1 and YAPcolocalize by fluorescence microscopy (View interaction)