Wip1 regulates Smad4 phosphorylation and inhibits TGF-? signaling

ABSTRACT: The tumor suppressor Smad4, a key mediator of the TGF-?/BMP pathways, is essential for development and tissue homeostasis. Phosphorylation of Smad4 in its linker region catalyzed by the mitogen-activated protein kinase (MAPK) plays a pivotal role in regulating its transcriptional activity and stability. In contrast, roles of Smad4 dephosphorylation as a control mechanism of TGF-?/BMP signaling and the phosphatases responsible for its dephosphorylation remain so far elusive. Here, we identify Wip1 as a Smad4 phosphatase. Wip1 selectively binds and dephosphorylates Smad4 at Thr277, a key MAPK phosphorylation site, thereby regulating its nuclear accumulation and half-life. In Xenopus embryos, Wip1 limits mesoderm formation and favors neural induction by inhibiting TGF-?/BMP signals. Wip1 rest

SUBMITTER: Dr. Dong-Seok Park 

PROVIDER: S-SCDT-EMBOR-2019-48693-T | biostudies-other |

REPOSITORIES: biostudies-other