Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway.

Abstract:

:YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study establishes a molecular mechanism and functional significance of AMPK in linking cellular energy status to the Hippo-YAP pathway.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Mo JS,Meng Z,Kim YC,Park HW,Hansen CG,Kim S,Lim DS,Guan KL

doi

10.1038/ncb3111

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

500-10

issue

4

eissn

1465-7392

issn

1476-4679

pii

ncb3111

journal_volume

17

pub_type

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