AJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol.
AJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol.
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DOI：
10.1128/mcb.00136-16
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发表时间：
2016-10-15
影响因子：
5.3
通讯作者：
Longmore GD
中科院分区：
文献类型：
--
作者：
Jagannathan R;Schimizzi GV;Zhang K;Loza AJ;Yabuta N;Nojima H;Longmore GD
河马途径控制着器官的生长，并与癌症的发展有关。河马途径的活性是否以及如何受到限制以维持或在需要时启动细胞生长尚不清楚。LIM蛋白AJUBA家族的成员是河马途径的负调节因子。在哺乳动物上皮细胞中，我们发现AJUBA Lim蛋白通过隔离胞浆中的河马激酶复合体来限制Hippo对YAP的调节，在增殖细胞中，LATS激酶被抑制。在生长受阻细胞的质膜上，AJUBA LIM蛋白不抑制或与河马激酶复合体结合。AJUBA LIM蛋白在果蝇翅膀发育过程中抑制河马对YAP的调节并与其结合的能力与其限制河马信号的能力直接相关。AJUBA LIM蛋白不影响YAP对细胞外在或细胞内机械信号的反应活性。因此，AJUBA LIM蛋白在需要细胞增殖的环境中限制河马途径的活性。
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.