Fig. 5. The Hippo signaling pathway is mediated by a kinase cascade and regulates cell proliferation and apoptosis. WW45 and LATS protein levels are maintained at low levels by NEDD4-mediated degradation, which confirms the OFF state of Hippo signaling pathway. YOD1 activates the Hippo pathway through repression of NEDD4. When activity of NEDD4 is inhibited by YOD1, YAP is phosphorylated by LATS1. At this time, YAP cannot enter into the nucleus and cell proliferation is inhibited.