The Hippo-Yes Association Protein Pathway in Liver Cancer
Figure 1
The Hippo pathway in Drosophila (a) and mammals (b). In the Drosophila, the upstream regulation factors exist in both surface membrane, such as Ds, Fat, and Crumbs, and submembrane proteins, such as Ex and Mer. The main effectors of Hippo pathway upstream are Hpo, Sav, Wts, and Mats, and the downstream effectors are Yki and Sd. In the mammals, the homologies of Drosophila in surface membrane protein are DCHS1-2, Ft1-4, and Crb1-3. The submembrane regulators are Nf2 and FROMD6. The Hippo pathway core machinery consists of Mst1/2, WW45, Lats1/2, and Mob1 and downstream effectors are YAP, TAZ, and TEADs. When surface membrane proteins are activated, they will activate subsequence effectors, which will then recruit Hippo core effectors to form complex, such as FRMD6-Nf2 and YAP-TAZ (Yki in Drosophila). Activated Hippo kinase complex will phosphorylate and then be inactivated through interaction with 14-3-3 proteins. Nonphosphorylated YAP/TAZ transfer into the nucleus, interact with TEADs (Sd in Drosophila), and then drive target gene expression to promote cell proliferation and suppress apoptosis.
