ArticleThe EMBO journal2017
USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 51 citations in OpenAlex.
- SMAD4 Palmitoylation Drives a Metabolic-Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation-driven USP4-mediated ANXA2 stabilization and activation promotes maintenance and radioresistance of glioblastoma stem cells.Cell death and differentiation · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- USP4 regulates ribosome biogenesis and protein synthesis for hematopoietic stem cell regeneration and leukemia progression.Leukemia · 2024Article
- Epidermal Growth Factor-Like Repeats and Discoidin I-Like Domains 3 Deficiency Attenuates Dilated Cardiomyopathy by Inhibiting Ubiquitin Specific Peptidase 10 Dependent Smad4 Deubiquitination.Journal of the American Heart Association · 2024Article
- Crosstalk between ubiquitination and translation in neurodevelopmental disorders.Frontiers in molecular neuroscience · 2024Review
- FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.PLoS biology · 2023Article
- Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12.Cell death & disease · 2023Article
- Ubiquitin-specific peptidases: Players in bone metabolism.Cell proliferation · 2023Review
- Xiaoaiping improves the general state of rats with malignant ascites secondary to gastric cancer by blocking the TGF-β1 signaling pathway.American journal of translational research · 2023Article
- TGF-beta signal transduction: biology, function and therapy for diseases.Molecular biomedicine · 2022Review
- Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia-reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination.Acta pharmaceutica Sinica. B · 2022Article
- Monoubiquitination in Homeostasis and Cancer.International journal of molecular sciences · 2022Review
- The E3 ubiquitin ligase SMURF2 stabilizes RNA editase ADAR1p110 and promotes its adenosine-to-inosine (A-to-I) editing function.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- UbiBrowser 2.0: a comprehensive resource for proteome-wide known and predicted ubiquitin ligase/deubiquitinase-substrate interactions in eukaryotic species.Nucleic acids research · 2022Article
- Ubiquitin modification in osteogenic differentiation and bone formation: From mechanisms to clinical significance.Frontiers in cell and developmental biology · 2022Review
- The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases.Reproductive sciences (Thousand Oaks, Calif.) · 2021Review
- Expression and Role of Ubiquitin-Specific Peptidases in Osteoblasts.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SMAD4 is a common intracellular effector for TGF-β family cytokines, but the mechanism by which its activity is dynamically regulated is unclear. We demonstrated that ubiquitin-specific protease (USP) 4 strongly induces activin/BMP signaling by removing the inhibitory monoubiquitination from SMAD4. This modification was triggered by the recruitment of the E3 ligase, SMURF2, to SMAD4 following ligand-induced regulatory (R)-SMAD-SMAD4 complex formation. Whereas the interaction of the negative regulator c-SKI inhibits SMAD4 monoubiquitination, the ligand stimulates the recruitment of SMURF2 to the c-SKI-SMAD2 complex and triggers c-SKI ubiquitination and degradation. Thus, SMURF2 has a role in termination and initiation of TGF-β family signaling. An increase in monoubiquitinated SMAD4 in USP4-depleted mouse embryonic stem cells (mESCs) decreased both the BMP- and activin-induced changes in the embryonic stem cell fate. USP4 sustained SMAD4 activity during activin- and BMP-mediated morphogenic events in early zebrafish embryos. Moreover, zebrafish depleted of USP4 exhibited defective cell migration and slower coordinated cell movement known as epiboly, both of which could be rescued by SMAD4. Therefore, USP4 is a critical determinant of SMAD4 activity.
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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.