ArticleProceedings of the National Academy of Sciences of the United States of America2010
Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- FOXO6 inhibits SMURF2-mediated ubiquitination and degradation of NR4A1 to promote retinal pigment epithelial cell ferroptosis in diabetic retinopathy.Journal of cell communication and signaling · 2026Article
- SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.International journal of molecular sciences · 2026Review
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Article
- Increased Kindlin-2 via SMURF1 Inhibition Attenuates Endothelial Permeability and Acute Lung Injury.International journal of molecular sciences · 2025Article
- Exploring Smad5: a review to pave the way for a deeper understanding of the pathobiology of common respiratory diseases.Molecular medicine (Cambridge, Mass.) · 2024Review
- Modulating binding affinity, specificity, and configurations by multivalent interactions.Biophysical journal · 2022Article
- The Twofold Role of Osteogenic Small Molecules in Parkinson's Disease Therapeutics: Crosstalk of Osteogenesis and Neurogenesis.BioMed research international · 2022Review
- The role of ubiquitination and deubiquitination in tumor invasion and metastasis.International journal of biological sciences · 2022Review
- New genotypes of Helicobacter Pylori VacA d-region identified from global strains.BMC molecular and cell biology · 2021Article
- E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation.Frontiers in cell and developmental biology · 2021Review
- Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.Frontiers in oncology · 2021Review
- Article
- Cooperative binding of the tandem WW domains of PLEKHA7 to PDZD11 promotes conformation-dependent interaction with tetraspanin 33.The Journal of biological chemistry · 2020Article
- The Effects of WW2/WW3 Domains of Smurf2 Molecule on CD4+CD25+/CD4+ Proportion in Spleen of 4T1 Tumor Bearing BALB/c Mice.Iranian biomedical journal · 2020Article
- Molecular recognition of ubiquitin and Lys63-linked diubiquitin by STAM2 UIM-SH3 dual domain: the effect of its linker length and flexibility.Scientific reports · 2019Article
- c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression.Nature communications · 2019Article
- Smad7 Binds Differently to Individual and Tandem WW3 and WW4 Domains of WWP2 Ubiquitin Ligase Isoforms.International journal of molecular sciences · 2019Article
- A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis.Cell reports · 2019Article
- Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity.eLife · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Smad ubiquitination regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that participates in degradation of TGF-β receptors and other targets. Smurf2 WW domains recognize PPXY (PY) motifs on ubiquitin ligase target proteins or on adapters, such as Smad7, that bind to E3 target proteins. We previously demonstrated that the isolated WW3 domain of Smurf2, but not the WW2 domain, can directly bind to a Smad7 PY motif. We show here that the WW2 augments this interaction by binding to the WW3 and making auxiliary contacts with the PY motif and a novel E/D-S/T-P motif, which is N-terminal to all Smad PY motifs. The WW2 likely enhances the selectivity of Smurf2 for the Smad proteins. NMR titrations confirm that Smad1 and Smad2 are bound by Smurf2 with the same coupled WW domain arrangement used to bind Smad7. The analogous WW domains in the short isoform of Smurf1 recognize the Smad7 PY peptide using the same coupled mechanism. However, a longer Smurf1 isoform, which has an additional 26 residues in the inter-WW domain linker, is only partially able to use the coupled WW domain binding mechanism. The longer linker results in a decrease in affinity for the Smad7 peptide. Interdomain coupling of WW domains enhances selectivity and enables the tuning of interactions by isoform switching.
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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.