Kindlin-2 Inhibits the Hippo Signaling Pathway by Promoting Degradation of MOB1

Publication date: 10 December 2019Source: Cell Reports, Volume 29, Issue 11Author(s): Jiagui Song, Tianzhuo Wang, Xiaochun Chi, Xiaofan Wei, Sidi Xu, Miao Yu, Huiying He, Ji Ma, Xueying Li, Juan Du, Xiaoran Sun, Yunling Wang, Jun Zhan, Hongquan ZhangSummaryThe Hippo signaling pathway plays a key role in development and cancer progression. However, molecules that intrinsically inhibit this pathway are less well known. Here, we report that the focal adhesion molecule Kindlin-2 inhibits Hippo signaling by interacting with and degrading MOB1 and promoting the interaction between MOB1 and the E3 ligase praja2. Kindlin-2 thus inhibits the phosphorylation of LATS1 and YAP and promotes YAP translocation into the nucleus, where it activates downstream Hippo target gene transcription. Kindlin-2 depletion activates Hippo/YAP signaling and alleviates renal fibrosis in Kindlin-2 knockout mice with unilateral ureteral occlusion (UUO). Moreover, Kindlin-2 levels are negatively correlated with MOB1 and phosphorylated (p) YAP in samples from patients with renal fibrosis. Altogether, these results demonstrate that Kindlin-2 inhibits Hippo signaling through degradation of MOB1. A specific long-lasting siRNA against Kindlin-2 effectively alleviated UUO-induced renal fibrosis and could be a potential therapy for renal fibrosis.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

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PMID: 31985642 [PubMed - in process]
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