AJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol

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  • Radhika Jagannathan
    The ICCE Institute, Washington University, St. Louis, Missouri, USA
  • Gregory V. Schimizzi
    The ICCE Institute, Washington University, St. Louis, Missouri, USA
  • Kun Zhang
    The ICCE Institute, Washington University, St. Louis, Missouri, USA
  • Andrew J. Loza
    The ICCE Institute, Washington University, St. Louis, Missouri, USA
  • Norikazu Yabuta
    Department of Molecular Genetics, Research Institute for Microbial Disease, Osaka University, Osaka, Japan
  • Hitoshi Nojima
    Department of Molecular Genetics, Research Institute for Microbial Disease, Osaka University, Osaka, Japan
  • Gregory D. Longmore
    The ICCE Institute, Washington University, St. Louis, Missouri, USA

書誌事項

公開日
2016-10-01
資源種別
journal article
権利情報
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1128/mcb.00136-16
公開者
Informa UK Limited

説明

The Hippo pathway controls organ growth and is implicated in cancer development. Whether and how Hippo pathway activity is limited to sustain or initiate cell growth when needed is not understood. The members of the AJUBA family of LIM proteins are negative regulators of the Hippo pathway. In mammalian epithelial cells, we found that AJUBA LIM proteins limit Hippo regulation of YAP, in proliferating cells only, by sequestering a cytosolic Hippo kinase complex in which LATS kinase is inhibited. At the plasma membranes of growth-arrested cells, AJUBA LIM proteins do not inhibit or associate with the Hippo kinase complex. The ability of AJUBA LIM proteins to inhibit YAP regulation by Hippo and to associate with the kinase complex directly correlate with their capacity to limit Hippo signaling during Drosophila wing development. AJUBA LIM proteins did not influence YAP activity in response to cell-extrinsic or cell-intrinsic mechanical signals. Thus, AJUBA LIM proteins limit Hippo pathway activity in contexts where cell proliferation is needed.

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