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 Bioljournal_title
Nature cell biologyauthors
Mo JS,Meng Z,Kim YC,Park HW,Hansen CG,Kim S,Lim DS,Guan KLdoi
10.1038/ncb3111subject
Has Abstractpub_date
2015-04-01 00:00:00pages
500-10issue
4eissn
1465-7392issn
1476-4679pii
ncb3111journal_volume
17pub_type
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