MST2 methylation by PRMT5 inhibits Hippo signaling and promotes pancreatic cancer progression.

ABSTRACT: The Hippo signaling axis is a tumor suppressor pathway that is activated by various extra-pathway factors to regulate cell differentiation and organ development. Recent studies have reported that autophosphorylation of the core kinase cassette stimulates activation of the Hippo signaling cascade. Here, we demonstrate that protein arginine methyltransferase 5 (PRMT5) contributes to inactivation of the Hippo signaling pathway in pancreatic cancer. We show that the Hippo pathway initiator serine/threonine kinase 3 (STK3, also known as MST2) of Hippo signaling pathway can be symmetrically di-methylated by PRMT5 at arginine-461 (R461) and arginine-467 (R467) in its SARAH domain. Methylation suppresses MST2 autophosphorylation and kinase activity by blocking its homodimerization, thereby inactiv

SUBMITTER: Sun Y 

PROVIDER: S-EPMC10690468 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature