Sav1 is a regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. It also plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, Sav1 activates the transcriptional activity of ESR1 through the modulation of its phosphorylation.
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Protein Aliases: 1700040G09Rik; 45 kDa WW domain protein; hWW45; mWW45; Protein salvador homolog 1; salvador homolog 1; WW domain-containing adaptor 45; WW domain-containing protein 3; WW domain-containing protein 4
Gene Aliases: 1700040G09Rik; Salv; SAV; SAV1; WW45; Wwp3; WWP4