Proteomics

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SDMA-shotgun analysis in pancreatic cancer cell lines


ABSTRACT: As a classic tumor suppressor pathway, Hippo signaling axis is activated by various extra-pathway factors to regulate cell differentiation and organ development. However, recent studies have reported that the activation of Hippo signaling pathway may be more dependent on the autophosphorylation of its core kinase cassette. Here, we demonstrate that protein arginine methyltransferase 5 (PRMT5) is involved in inducing the inactivation of Hippo signaling pathway in pancreatic cancer. Our study shows that the initiator serine/threonine kinase 3 (STK3, also known as MST2) of Hippo signaling pathway can be symmetrically di-methylated at arginine-461 (R461) and arginine-467 (R467) in the SARAH domain by PRMT5, and the methylated MST2 suppresses its autophosphorylation and kinase activity by blocking the formation of homodimer, thereby inactivating Hippo signaling pathway in pancreatic cancer. Moreover, we also discover that the specific PRMT5 inhibitor GSK3326595 re-activates the dysregulated Hippo signaling pathway

ORGANISM(S): Homo Sapiens

SUBMITTER: Heshui Wu  

PROVIDER: PXD044671 | iProX | Fri Aug 18 00:00:00 BST 2023

REPOSITORIES: iProX

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Publications

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

Sun Yan Y   Jin Xin X   Meng Junpeng J   Guo Feng F   Chen Taoyu T   Zhao Xiaoyan X   Wu Heshui H   Ren Dianyun D  

The EMBO journal 20231031 23


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/th  ...[more]

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