AJUBA LIM proteins limit Hippo activity in proliferating cells by sequestering the Hippo core kinase complex in the cytosol

Radhika Jagannathan, Gregory V. Schimizzi, Kun Zhang, Andrew J. Loza, Norikazu Yabuta, Hitoshi Nojima, Gregory D. Longmore

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)2526-2542
Number of pages17
JournalMolecular and cellular biology
Volume36
Issue number20
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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