ArticleThe Journal of biological chemistry2010
Calcium activates Nedd4 E3 ubiquitin ligases by releasing the C2 domain-mediated auto-inhibition.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins.Biomolecules · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment.Anti-cancer agents in medicinal chemistry · 2026Review
- Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK.The Journal of physiology · 2025Article
- Structural basis of ubiquitin ligase Nedd4-2 autoinhibition and regulation by calcium and 14-3-3 proteins.Nature communications · 2025Article
- Pharmacologically enabling the degradation of Na V 1.8 channels to reduce neuropathic pain.Pain · 2025Article
- TheFrontiers in plant science · 2025Article
- The Nedd4L ubiquitin ligase is activated by FCHO2-generated membrane curvature.The EMBO journal · 2024Article
- Article
- Aberrant expression of NEDD4L disrupts mitochondrial homeostasis by downregulating CaMKKβ in diabetic kidney disease.Journal of translational medicine · 2024Article
- Regulation of the water channel aquaporin-2 by cullin E3 ubiquitin ligases.American journal of physiology. Renal physiology · 2024Article
- LITAF protects against pore-forming protein-induced cell death by promoting membrane repair.Science immunology · 2024Article
- Portrait of WWP1: the current state in human cancer.Frontiers in cell and developmental biology · 2024Review
- WWP1 E3 ligase at the crossroads of health and disease.Cell death & disease · 2023Review
- Primate-specific isoform of Nedd4-1 regulates substrate binding via Ser/Thr phosphorylation and 14-3-3 binding.Scientific reports · 2023Article
- Discovery of Nedd4 auto-ubiquitination inhibitors.Scientific reports · 2023Article
- E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2.EMBO reports · 2022Article
- Diltiazem inhibits breast cancer metastasis via mediating growth differentiation factor 15 and epithelial-mesenchymal transition.Oncogenesis · 2022Article
- Elevated intracellular NaProceedings of the National Academy of Sciences of the United States of America · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nedd4 E3 ligases are members of the HECT E3 ubiquitin ligase family and regulate ubiquitination-mediated protein degradation. In this report, we demonstrate that calcium releases the C2 domain-mediated auto-inhibition in both Nedd4-1 and Nedd4-2. Calcium disrupts binding of the C2 domain to the HECT domain. Consistent with this, calcium activates the E3 ubiquitin ligase activity of Nedd4. Elevation of intracellular calcium by ionomycin treatment, or activation of acetylcholine receptor or epidermal growth factor receptor by carbachol or epidermal growth factor stimulation induced activation of endogenous Nedd4 in vivo evaluated by assays of either Nedd4 E3 ligase activity or ubiquitination of Nedd4 substrate ENaC-beta. The activation effect of calcium on Nedd4 E3 ligase activity was dramatically enhanced by a membrane-rich fraction, suggesting that calcium-mediated membrane translocation through the C2 domain might be an activation mechanism of Nedd4 in vivo. Our studies have revealed an activation mechanism of Nedd4 E3 ubiquitin ligases and established a connection of intracellular calcium signaling to regulation of protein ubiquitination.
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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.