Background
Salvador homolog, originally named WW45, was first identified as a 45 kDa protein containing a pair of WW domains and a coiled-coil region. SAV1 was subsequently shown to function as a scaffold protein, in a protein complex that includes the kinases MST2 and LATS1, and the transcriptional co-activator YAP. This protein complex comprises the core components of the Hippo signaling pathway, which regulates important cellular functions, including contact inhibition and apoptosis, that function to regulate tissue growth and organ size. A genetic screen in Drosophila identified a role for SAV1 in cell cycle regulation and apoptosis, while embryonic mice lacking Sav1 displayed hyperplastic growth and epithelial differentiation effects. These findings, together with the observation that SAV1 is mutated a number of human cancer cell lines, suggest that SAV1 functions as a tumor suppressor in the Hippo signaling pathway.
References
[1] Valverde, P. (2000) Biochem Biophys Res Commun 276, 990-8.
[2] Oka, T. et al. (2008) J Biol Chem 283, 27534-46.
[3] Guo, C. et al. (2007) Curr Biol 17, 700-5.
[4] Zeng, Q. and Hong, W. (2008) Cancer Cell 13, 188-92.
[5] Tapon, N. et al. (2002) Cell 110, 467-78.
[6] Lee, J.H. et al. (2008) EMBO J 27, 1231-42.
[7] Donninger, H. et al. (2011) J Biol Chem 286, 18483-91.
