ArticlePLoS pathogens2020
Essential roles for deubiquitination in Leishmania life cycle progression.
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 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.PLoS neglected tropical diseases · 2024Pooled it
- Towards precision antileishmanial drug discovery: Integrating multi-omics, functional genomics, artificial intelligence and host-directed therapeutics.Molecular biology reports · 2026Review
- Bi-directional highways and super-seeder tissues underpin parasite dissemination in experimental Leishmania donovani infection.Nature communications · 2026Article
- Five-layer systems analysis ofeLife · 2026Article
- A comprehensive review of CRISPR-Cas9-mediated genome editing in Leishmania strains: methodologies, applications, challenges and future directions.Molecular biology reports · 2026Review
- Article
- Quantitative proteomics of infected macrophages reveals novel Leishmania virulence factors.PLoS pathogens · 2026Article
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Genetic Manipulation Tools in Leishmania: From CRISPR/Cas9 to Vaccine Strategies for Disease Control.Acta parasitologica · 2025Review
- Novel Chalcone Derivatives as Anti-Antibiotics (Basel, Switzerland) · 2025Article
- Structure and activity of the essential UCH family deubiquitinase DUB16 from Leishmania donovani.The Biochemical journal · 2025Article
- Article
- Determination of key hub genes in Leishmaniasis as potential factors in diagnosis and treatment based on a bioinformatics study.Scientific reports · 2024Article
- Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.PLoS pathogens · 2024Article
- Recent Advances in CRISPR/Cas9-Mediated Genome Editing in Leishmania Strains.Acta parasitologica · 2024Review
- Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery.ACS bio & med chem Au · 2023Review
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics.Communications biology · 2022Article
- Bromodomain factor 5 is an essential regulator of transcription in Leishmania.Nature communications · 2022Article
- Transcriptome-Wide Identification of Coding and Noncoding RNA-Binding Proteins Defines the Comprehensive RNA Interactome of Leishmania mexicana.Microbiology spectrum · 2022Article
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10 authors.
Funding
Abstract
The parasitic protozoan Leishmania requires proteasomal, autophagic and lysosomal proteolytic pathways to enact the extensive cellular remodelling that occurs during its life cycle. The proteasome is essential for parasite proliferation, yet little is known about the requirement for ubiquitination/deubiquitination processes in growth and differentiation. Activity-based protein profiling of L. mexicana C12, C19 and C65 deubiquitinating cysteine peptidases (DUBs) revealed DUB activity remains relatively constant during differentiation of procyclic promastigote to amastigote. However, when life cycle phenotyping (bar-seq) was performed on a pool including 15 barcoded DUB null mutants created in promastigotes using CRISPR-Cas9, significant loss of fitness was observed during differentiation and intracellular infection. DUBs 4, 7, and 13 are required for successful transformation from metacyclic promastigote to amastigote and DUBs 3, 5, 6, 8, 10, 11 and 14 are required for normal amastigote proliferation in mice. DUBs 1, 2, 12 and 16 are essential for promastigote viability and the essential role of DUB2 in establishing infection was demonstrated using DiCre inducible gene deletion in vitro and in vivo. DUB2 is found in the nucleus and interacts with nuclear proteins associated with transcription/chromatin dynamics, mRNA splicing and mRNA capping. DUB2 has broad linkage specificity, cleaving all the di-ubiquitin chains except for Lys27 and Met1. Our study demonstrates the crucial role that DUBs play in differentiation and intracellular survival of Leishmania and that amastigotes are exquisitely sensitive to disruption of ubiquitination homeostasis.
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