Actin cytoskeleton regulates Hippo signaling.
Actin cytoskeleton regulates Hippo signaling.
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DOI：
10.1371/journal.pone.0073763
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hsueh AJ
中科院分区：
文献类型：
--
作者：
Reddy P;Deguchi M;Cheng Y;Hsueh AJ
Hippo通路通过调节细胞增殖和凋亡来控制器官大小。然而，肌动蛋白细胞骨架对hippo信号的上游调控尚不清楚。为了阐明肌动蛋白作为Hippo信号的上游调节因子的作用，使用一种肌动蛋白稳定药物茉莉素内酯提高了细胞中F（丝状）肌动蛋白的水平。在HeLa细胞中诱导F-actin形成导致Hippo信号传导的关键效应分子YAP磷酸化降低。激活的YAP定位于细胞核，YAP的增加与下游CCN生长因子CCN1/CYR61和CCN2/CTGF的表达增加有关。当YAP“敲低”细胞中的YAP水平受到抑制时，肌动蛋白稳定药物的作用被阻断。总之，通过使用肌动蛋白稳定药物，我们发现肌动蛋白细胞骨架是Hippo信号的上游调节因子之一，能够激活YAP并增加其下游CCN生长因子。
Hippo pathway controls the organ size by modulating cell proliferation and apoptosis. However, the upstream regulation of hippo signaling by actin cytoskeleton is not clear. To elucidate the role of actin as an upstream regulator of Hippo signaling, the levels of F (filamentous)-actin in cells were elevated using jasplakinolide, an actin-stabilizing drug. Induction of F-actin formation in HeLa cells resulted in decreased phosphorylation of YAP, a key effector molecule for Hippo signaling. The activated YAP is localized to the cell nucleus and YAP increase was associated with increased expression of downstream CCN growth factors CCN1/CYR61 and CCN2/CTGF. The effect of the actin-stabilizing drug was blocked when YAP levels were suppressed in YAP “knock-down” cells. In summary, using an actin-stabilizing drug we show that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
--
作者：
Miller, Eric;Yang, Jiayi;Wu, Xu
通讯作者：
Wu, Xu
影响因子：
64.5
作者：
Yu FX;Zhao B;Panupinthu N;Jewell JL;Lian I;Wang LH;Zhao J;Yuan H;Tumaneng K;Li H;Fu XD;Mills GB;Guan KL
通讯作者：
Guan KL
影响因子：
64.5
作者：
Harvey, KF;Pfleger, CM;Hariharan, IK
通讯作者：
Hariharan, IK
影响因子：
4.6
作者：
Fernandez, Beatriz Garcia;Gaspar, Pedro;Janody, Florence
通讯作者：
Janody, Florence