ArticleNature methods2020
Targeted deubiquitination rescues distinct trafficking-deficient ion channelopathies.
Article in Nature methods, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- A bifunctional actuator to correct loss-of-function deficits in cardiac voltage-gated sodium channels.Science advances · 2026Article
- Tiered modelling of a CACNA1A D1634N mutation linked to ataxia, epilepsy and cognitive deficits.Brain : a journal of neurology · 2026Article
- Targeted recruitment of USP15 enhances CTLA4 surface levels and restricts its degradation.Life science alliance · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Mapping the Functional Landscape ofmedRxiv : the preprint server for health sciences · 2025Article
- Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.Nature communications · 2025Article
- Development of an allosteric adhesion GPCR nanobody with therapeutic potential.Nature chemical biology · 2025Article
- Programmable protein stabilization with language model-derived peptide guides.Nature communications · 2025Article
- Deubiquitinase-Targeting Chimeras (DUBTACs) as a Potential Paradigm-Shifting Drug Discovery Approach.Journal of medicinal chemistry · 2025Review
- Nanobody-thioesterase chimeras to specifically target protein palmitoylation.Nature communications · 2025Article
- Small molecule-mediated targeted protein degradation of voltage-gated sodium channels involved in pain.bioRxiv : the preprint server for biology · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Targeting the ICirculation research · 2024Article
- Hyperactivation of ATF4/TGF-β1 signaling contributes to the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy caused by DSG2 Variant.BMC medicine · 2024Article
- Programmable Protein Stabilization with Language Model-Derived Peptide Guides.Research square · 2024Article
- USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT.Cancer cell international · 2024Article
- Ion channel trafficking implications in heart failure.Frontiers in cardiovascular medicine · 2024Review
- Splice-switching antisense oligonucleotides for pediatric neurological disorders.Frontiers in molecular neuroscience · 2024Review
- Cellular Assays for Dynamic Quantification of Deubiquitinase Activity and Inhibition.Journal of molecular biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Impaired protein stability or trafficking underlies diverse ion channelopathies and represents an unexploited unifying principle for developing common treatments for otherwise dissimilar diseases. Ubiquitination limits ion channel surface density, but targeting this pathway for the purposes of basic study or therapy is challenging because of its prevalent role in proteostasis. We developed engineered deubiquitinases (enDUBs) that enable selective ubiquitin chain removal from target proteins to rescue the functional expression of disparate mutant ion channels that underlie long QT syndrome (LQT) and cystic fibrosis (CF). In an LQT type 1 (LQT1) cardiomyocyte model, enDUB treatment restored delayed rectifier potassium currents and normalized action potential duration. CF-targeted enDUBs synergistically rescued common (ΔF508) and pharmacotherapy-resistant (N1303K) CF mutations when combined with the US Food and Drug Administation (FDA)-approved drugs Orkambi (lumacaftor/ivacaftor) and Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor). Altogether, targeted deubiquitination via enDUBs provides a powerful protein stabilization method that not only corrects diverse diseases caused by impaired ion channel trafficking, but also introduces a new tool for deconstructing the ubiquitin code in situ.
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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.