ArticleMolecular systems biology2009
Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays.
Article in Molecular systems biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 158 citations in OpenAlex.
- A guide to mapping ubiquitin and ubiquitin-like E3 ligases to their substrates.The FEBS journal · 2026Review
- Identification and validation of an interaction between the E3 ubiquitin ligase WWP1 and the Transcriptional Co-Activator WBP2 in the human heart.Biology open · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.Nature communications · 2025Article
- The ubiquitin ligase Nedd4-2 promotes localization of DNMBP/Tuba to P-bodies under hyperosmotic stress.The Journal of biological chemistry · 2025Article
- Optimum level of NEDD4 and its interaction with nsP3 are crucial to facilitate efficient Chikungunya virus (CHIKV) infection.The Journal of general virology · 2025Article
- The primate-specific Nedd4-1(NE) localizes to late endosomes in response to amino acids to suppress autophagy.Nature communications · 2025Article
- K27-linked RORγt ubiquitination by Nedd4 potentiates Th17-mediated autoimmunity.Journal of biomedical science · 2025Article
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
- Article
- NEDD4-2 and the CLC-2 channel regulate neuronal excitability in the pathogenesis of mesial temporal lobe epilepsy.Scientific reports · 2024Article
- Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell.Nature communications · 2024Article
- Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity.The Journal of cell biology · 2024Article
- Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers.Nature communications · 2023Article
- Primate-specific isoform of Nedd4-1 regulates substrate binding via Ser/Thr phosphorylation and 14-3-3 binding.Scientific reports · 2023Article
- TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.Cell reports · 2023Article
- Discovery of Nedd4 auto-ubiquitination inhibitors.Scientific reports · 2023Article
- Review
- Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Target recognition by the ubiquitin system is mediated by E3 ubiquitin ligases. Nedd4 family members are E3 ligases comprised of a C2 domain, 2-4 WW domains that bind PY motifs (L/PPxY) and a ubiquitin ligase HECT domain. The nine Nedd4 family proteins in mammals include two close relatives: Nedd4 (Nedd4-1) and Nedd4L (Nedd4-2), but their global substrate recognition or differences in substrate specificity are unknown. We performed in vitro ubiquitylation and binding assays of human Nedd4-1 and Nedd4-2, and rat-Nedd4-1, using protein microarrays spotted with approximately 8200 human proteins. Top hits (substrates) for the ubiquitylation and binding assays mostly contain PY motifs. Although several substrates were recognized by both Nedd4-1 and Nedd4-2, others were specific to only one, with several Tyr kinases preferred by Nedd4-1 and some ion channels by Nedd4-2; this was subsequently validated in vivo. Accordingly, Nedd4-1 knockdown or knockout in cells led to sustained signalling via some of its substrate Tyr kinases (e.g. FGFR), suggesting Nedd4-1 suppresses their signalling. These results demonstrate the feasibility of identifying substrates and deciphering substrate specificity of mammalian E3 ligases.
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Registered trials
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