ArticleThe EMBO journal1997
Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
246 citing papers in PubMed, 700 citations in OpenAlex.
- Monogenic Kidney Disorders as Hidden Drivers of Electrolyte Imbalance and Hypertension.Electrolyte & blood pressure : E & BP · 2026Review
- Congenital aldosterone deficiency and its resistance.Endocrine journal · 2026Review
- Review
- Lack of intestinal Mucin-1 impairs intestinal epithelial barrier and promotes metabolic dysfunction-associated steatotic liver disease in male mice.Nature communications · 2025Article
- The scaffold protein IQGAP1 regulates the epithelial NaThe Journal of biological chemistry · 2025Article
- Acute activation of human epithelial sodium channel (ENaC) by serum and glucocorticoid inducible kinase 1 (SGK1) requires prior cleavage of the channel's γ-subunit at its proximal cleavage site.Pflugers Archiv : European journal of physiology · 2025Article
- SECS, drugs, and Rac1&Rho: regulation of EnNaC in vascular endothelial cells.Pflugers Archiv : European journal of physiology · 2025Article
- Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.American journal of physiology. Cell physiology · 2025Article
- Case Report: Functional investigation of the γENaC G532S mutation presenting as mild PHA-1B3.Frontiers in medicine · 2025Article
- Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway.International journal of molecular sciences · 2024Article
- Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance.Molecular biology of the cell · 2024Article
- Control of ENaC ubiquitination.American journal of physiology. Renal physiology · 2024Article
- Review
- Epithelial NaComprehensive Physiology · 2024Review
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia.American journal of physiology. Cell physiology · 2024Article
- The Role of Ion-Transporting Proteins in Human Disease.International journal of molecular sciences · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- LITAF protects against pore-forming protein-induced cell death by promoting membrane repair.Science immunology · 2024Article
- Article
186 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epithelial Na+ channel (ENaC), composed of three subunits (alpha beta gamma), plays a critical role in salt and fluid homeostasis. Abnormalities in channel opening and numbers have been linked to several genetic disorders, including cystic fibrosis, pseudohypoaldosteronism type I and Liddle syndrome. We have recently identified the ubiquitin-protein ligase Nedd4 as an interacting protein of ENaC. Here we show that ENaC is a short-lived protein (t1/2 approximately 1 h) that is ubiquitinated in vivo on the alpha and gamma (but not beta) subunits. Mutation of a cluster of Lys residues (to Arg) at the N-terminus of gamma ENaC leads to both inhibition of ubiquitination and increased channel activity, an effect augmented by N-terminal Lys to Arg mutations in alpha ENaC, but not in beta ENaC. This elevated channel activity is caused by an increase in the number of channels present at the plasma membrane; it represents increases in both cell-surface retention or recycling of ENaC and incorporation of new channels at the plasma membrane, as determined by Brefeldin A treatment. In addition, we find that the rapid turnover of the total pool of cellular ENaC is attenuated by inhibitors of both the proteasome and the lysosomal/endosomal degradation systems, and propose that whereas the unassembled subunits are degraded by the proteasome, the assembled alpha beta gamma ENaC complex is targeted for lysosomal degradation. Our results suggest that ENaC function is regulated by ubiquitination, and propose a paradigm for ubiquitination-mediated regulation of ion channels.
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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.