Regulation of hWW45 protein stability by MST1 in vivo

Abstract

Establishing and maintaining homeostasis can be determined by the balance of cell proliferation and death. Two genes that are involved in regulation of growth, proliferation and apoptosis in Drosophila are hippo (Hpo), encoding a serine/threonine kinase, and Salvador (Sav), encoding a coiled coil domain. Human counterparts of these genes, MST1 and hWW45 respectively, have been found to be frequently down-regulated or deleted in cancers, but their molecular implications in tumorigenesis are still obscure. In the present study, we demonstrate that hWW45 interacts with MST1 (mammalian sterile20-like kinase), and that MST1 is able to phosphorylate hWW45 c-terminal region including SARAH domain. In addition to binding and phosphorylation, we show that the stability of hWW45 is increased by co-expression with MST1, and that the level of endogenous hWW45 protein is also significantly decreased in MST1-depleted cell. However, unlike the case of fruit fly, the MST1 dependent phosphorylation of hWW45 doesn``t have any effect on its stability. Based on our observations, we propose that the stability of hWW45 protein might be regulated by MST1 in vivo.