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

Research paper by Radhika R Jagannathan, Gregory V GV Schimizzi, Kun K Zhang, Andrew J AJ Loza, Norikazu N Yabuta, Hitoshi H Nojima, Gregory D GD Longmore

Indexed on: 28 Jul '16Published on: 28 Jul '16Published in: Molecular and cellular biology



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 AJUBA family of LIM proteins are negative regulators of the Hippo pathway. In mammalian epithelial cells we find that AJUBA LIM proteins limit Hippo regulation of YAP, only in proliferating cells, by sequestering a cytosolic Hippo kinase complex in which LATS kinase is inhibited. At the plasma membrane 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 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.