ArticleEMBO reports2020
Wip1 regulates Smad4 phosphorylation and inhibits TGF-β signaling.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth.Cell death & disease · 2025Article
- Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer.Cancer biology & therapy · 2024Review
- PP2C phosphatases-terminators of suicidal thoughts.Cell death & disease · 2024Review
- SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.American journal of human genetics · 2024Article
- Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a.Cellular & molecular immunology · 2023Article
- KRAS mutation-induced EndMT of brain arteriovenous malformation is mediated through the TGF-β/BMP-SMAD4 pathway.Stroke and vascular neurology · 2023Article
- Ethanol Effects on Early Developmental Stages Studied Using the Zebrafish.Biomedicines · 2022Review
- PPM1D in Solid and Hematologic Malignancies: Friend and Foe?Molecular cancer research : MCR · 2022Article
- Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia.Stroke and vascular neurology · 2021Article
- Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.PloS one · 2021Article
- The Role of TGF-Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Review
- Wip1 regulates Smad4 phosphorylation and inhibits TGF-β signaling.EMBO reports · 2020Article
- Controlling Smad4 signaling with a Wip.EMBO reports · 2020Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
The tumor suppressor Smad4, a key mediator of the TGF-β/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-β/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-β/BMP signals. Wip1 restrains TGF-β-induced growth arrest, migration, and invasion in human cells and enhances the tumorigenicity of cancer cells by repressing the antimitogenic activity of Smad4. We propose that Wip1-dependent dephosphorylation of Smad4 is critical for the regulation of TGF-β signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.