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

TitleAJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol.
Publication TypeJournal Article
Year of Publication2016
AuthorsJagannathan R, Schimizzi GV, Zhang K, Loza AJ, Yabuta N, Nojima H, Longmore GD
JournalMol Cell Biol
Volume36
Issue20
Pagination2526-42
Date Published2016 10 15
ISSN1098-5549
KeywordsAdaptor Proteins, Signal Transducing, Animals, Cell Proliferation, Cytosol, Drosophila melanogaster, Drosophila Proteins, Epithelial Cells, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins, LIM Domain Proteins, MCF-7 Cells, Phosphoproteins, Protein-Serine-Threonine Kinases, Signal Transduction, Transcription Factors, Wings, Animal
Abstract

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.

DOI10.1128/MCB.00136-16
Alternate JournalMol. Cell. Biol.
PubMed ID27457617
PubMed Central IDPMC5038147
Grant ListT32 GM007200 / GM / NIGMS NIH HHS / United States
R01 GM080673 / GM / NIGMS NIH HHS / United States
T32 EB018266 / EB / NIBIB NIH HHS / United States
F30 CA180244 / CA / NCI NIH HHS / United States
R01 CA196205 / CA / NCI NIH HHS / United States

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