ArticlePLoS pathogens2020
COP9 signalosome is an essential and druggable parasite target that regulates protein degradation.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs.Journal of medicinal chemistry · 2026Review
- Amebiasis as a neglected tropical disease: Current knowledge gaps and future directions.PLoS neglected tropical diseases · 2026Review
- Exploration of innovative drug repurposing strategies for combating human protozoan diseases: Advances, challenges, and opportunities.Journal of pharmaceutical analysis · 2025Review
- The Toxoplasma gondii F-Box Protein L2 Functions as a Repressor of Stage Specific Gene Expression.PLoS pathogens · 2024Article
- Weighted gene co-expression network analysis reveals immune evasion related genes inExperimental biology and medicine (Maywood, N.J.) · 2024Article
- Disulfiram: Mechanisms, Applications, and Challenges.Antibiotics (Basel, Switzerland) · 2023Review
- Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery.ACS bio & med chem Au · 2023Review
- Alcohol Abuse Drug Disulfiram Is Effective against Cyst Stages of Entamoeba histolytica Parasite.Antimicrobial agents and chemotherapy · 2022Article
- A time-resolved multi-omics atlas of Acanthamoeba castellanii encystment.Nature communications · 2022Article
- Ponatinib, Lestaurtinib, and mTOR/PI3K Inhibitors Are Promising Repurposing Candidates against Entamoeba histolytica.Antimicrobial agents and chemotherapy · 2022Article
- Novel dithiocarbamate derivatives are effective copper-dependent antimicrobials againstFrontiers in microbiology · 2022Article
- An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives.Frontiers in cellular and infection microbiology · 2022Review
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
- The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.Frontiers in cellular and infection microbiology · 2022Review
- Identification ofFrontiers in cellular and infection microbiology · 2022Article
- Drug Repurposing of the Alcohol Abuse Medication Disulfiram as an Anti-Parasitic Agent.Frontiers in cellular and infection microbiology · 2021Article
- Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis.Frontiers in cellular and infection microbiology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Understanding how the protozoan protein degradation pathway is regulated could uncover new parasite biology for drug discovery. We found the COP9 signalosome (CSN) conserved in multiple pathogens such as Leishmania, Trypanosoma, Toxoplasma, and used the severe diarrhea-causing Entamoeba histolytica to study its function in medically significant protozoa. We show that CSN is an essential upstream regulator of parasite protein degradation. Genetic disruption of E. histolytica CSN by two distinct approaches inhibited cell proliferation and viability. Both CSN5 knockdown and dominant negative mutation trapped cullin in a neddylated state, disrupting UPS activity and protein degradation. In addition, zinc ditiocarb (ZnDTC), a main metabolite of the inexpensive FDA-approved globally-available drug disulfiram, was active against parasites acting in a COP9-dependent manner. ZnDTC, given as disulfiram-zinc, had oral efficacy in clearing parasites in vivo. Our findings provide insights into the regulation of parasite protein degradation, and supports the significant therapeutic potential of COP9 inhibition.
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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.