| First Author | Song J | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 11 | Pages | 3664-3677.e5 |
| PubMed ID | 31825843 | Mgi Jnum | J:296751 |
| Mgi Id | MGI:6468813 | Doi | 10.1016/j.celrep.2019.11.035 |
| Citation | Song J, et al. (2019) Kindlin-2 Inhibits the Hippo Signaling Pathway by Promoting Degradation of MOB1. Cell Rep 29(11):3664-3677.e5 |
| abstractText | The 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. |
