ArticleProceedings of the National Academy of Sciences of the United States of America2017
Deubiquitinating enzyme VCIP135 dictates the duration of botulinum neurotoxin type A intoxication.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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
36 citing papers in PubMed, 55 citations in OpenAlex.
- The Use of Botulinum Toxin in the Management of Headache Disorders.Handbook of experimental pharmacology · 2021Trial
- TrenibotulinumtoxinE: Pharmacology, clinical evidence, and emerging role in aesthetic medicine.JPRAS open · 2026Review
- Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- VCPIP1 drives diabetic cardiomyopathy by deubiquitinating AMPKγ1 and preventing AMPKα-γ subunit assembly in cardiomyocytes.Signal transduction and targeted therapy · 2026Article
- Advances in Clostridial Neurotoxins: Passage of the Intestinal Barrier and Targeting of Specific Neuronal Cells.Toxins · 2026Review
- Phosphorylation of SNAP-25 at Ser187 is enhanced following its cleavage by Botulinum Neurotoxin Serotype A, promoting the dominant-negative effect of the resulting fragment.PLoS pathogens · 2025Article
- Article
- Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Insights from 25 years of onabotulinumtoxinA in migraine - mechanisms and management.Nature reviews. Neurology · 2024Review
- Ubiquitin-Proteasome System in the Different Stages of Dominantly Inherited Alzheimer's Disease.Research square · 2024Article
- The Degradation of Botulinum Neurotoxin Light Chains Using PROTACs.International journal of molecular sciences · 2024Article
- Review
- Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications.Toxins · 2024Review
- Article
- Comprehensive list of preventative migraine headache medications without significant drug-drug interactions.Frontiers in neurology · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Botox (onabotulinumtoxinA) mechanism of action.Medicine · 2023Article
- Characterization of Serotype CD Mosaic Botulinum Neurotoxin in Comparison with Serotype C and A.Toxins · 2023Article
- A Comprehensive Structural Analysis ofToxins · 2023Review
- Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications.Toxins · 2022Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Botulism is characterized by flaccid paralysis, which can be caused by intoxication with any of the seven known serotypes of botulinum neurotoxin (BoNT), all of which disrupt synaptic transmission by endoproteolytic cleavage of SNARE proteins. BoNT serotype A (BoNT/A) has the most prolonged or persistent effects, which can last several months, and exerts its effects by specifically cleaving and inactivating SNAP25. A major factor contributing to the persistence of intoxication is the long half-life of the catalytic light chain, which remains enzymatically active months after entry into cells. Here we report that BoNT/A catalytic light chain binds to, and is a substrate for, the ubiquitin ligase HECTD2. However, the light chain evades proteasomal degradation by the dominant effect of a deubiquitinating enzyme, VCIP135/VCPIP1. This deubiquitinating enzyme binds BoNT/A light chain directly, with the two associating in cells through the C-terminal 77 amino acids of the light chain protease. The development of specific DUB inhibitors, together with inhibitors of BoNT/A proteolytic activity, may be useful for reducing the morbidity and public health costs associated with BoNT/A intoxication and could have potential biodefense implications.
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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.