Salvador homolog 1 (SAV1)

Salvador homolog 1 (SAV1) is a scaffold/adaptor protein containing two WW domains and a coiled-coil region, conserved in mammals and flies[3][4]. It is a core regulator of the Hippo signaling pathway, required for activation of the serine/threonine kinases MST1 and MST2 (also called STK3/4), which promotes cell-cycle exit and terminal differentiation. SAV1 binds MST1/2 via its SARAH domain, stabilizes kinase complexes, and facilitates phosphorylation of downstream targets (LATS1/2 and YAP/TAZ), thereby restraining cell proliferation and promoting apoptosis[1][2][4]. Loss or deficiency of SAV1 disrupts Hippo signaling and is linked with increased tumorigenesis, metastasis, and poor clinical outcomes. SAV1 also directly inhibits AKT phosphorylation and can suppress Hedgehog signaling. In humans, the SAV1 gene is rarely mutated, but its expression is frequently downregulated in cancer via epigenetic or post-transcriptional mechanisms. Experimental drugs such as lycorine can upregulate SAV1 expression and may have therapeutic potential[1][2]. Key molecular features: - Two WW domains - SARAH domain - Coiled-coil region - Ubiquitously expressed across adult tissues[3][4]

Other names

WW45SAV1Protein salvador homolog 1

Scaffold/adaptor for MST1/2 (Hippo kinases), promotes kinase activation and phosphorylation cascade that regulates YAP and TAZ oncogenic activity, inhibition of AKT phosphorylation, inhibition of oncogenic transcriptional programs