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

Research output: Contribution to journalArticle

  • Jung-Soon Mo
  • Zhipeng Meng
  • Young Chul Kim
  • Hyun Woo Park
  • Carsten Gram Hansen
  • Soohyun Kim
  • Dae-Sik Lim
  • Kun-Liang Guan

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Original languageEnglish
Pages (from-to)500-10
Number of pages11
JournalNature Cell Biology
Volume17
Issue number4
DOIs
StatePublished - Apr 2015

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.

    Research areas

  • 3T3 Cells, AMP-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Animals, Cell Line, Cell Transformation, Neoplastic, Cytoplasm, DNA-Binding Proteins, Energy Metabolism, Enzyme Activation, HEK293 Cells, HeLa Cells, Humans, Mice, Mice, Nude, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein-Serine-Threonine Kinases, RNA Interference, RNA, Small Interfering, Transcription Factors

ID: 24501723