ArticlePLoS pathogens2024
Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrity.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Protist oxygen-sensing and the role of prolyl hydroxylase-regulation of E3(SCF) ubiquitin ligases.Biochimica et biophysica acta. General subjects · 2026Review
- The Putative E3 Ubiquitin Ligase TEX1 Is Required for Nuclear Biology and Developmental Progression ofCells · 2026Article
- Evolution, composition and functions of cullin E3 ubiquitin ligases in trypanosomes.Scientific reports · 2025Article
- Glycoregulation of E3(SCF) ubiquitin ligases in unicellular eukaryotes.Glycobiology · 2025Review
- An ER-resident lipid scramblase is crucial for biogenesis and function of apicomplexan parasite secretory organelles.Nature communications · 2025Article
- Variation in Gene Expression Across Infection Status and Elevation in a Hawaiian Honeycreeper.Ecology and evolution · 2025Article
- Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes.Scientific reports · 2025Article
- PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages.Communications biology · 2025Article
- Overexpression inFrontiers in cellular and infection microbiology · 2025Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Protein ubiquitination is essential for cellular homeostasis and regulation of several processes, including cell division and genome integrity. Ubiquitin E3 ligases determine substrate specificity for ubiquitination, and Cullin-RING E3 ubiquitin ligases (CRLs) make the largest group among the ubiquitin E3 ligases. Although conserved and most studied in model eukaryotes, CRLs remain underappreciated in Plasmodium and related parasites. To investigate the CRLs of human malaria parasite Plasmodium falciparum, we generated parasites expressing tagged P. falciparum cullin-1 (PfCullin-1), cullin-2 (PfCullin-2), Rbx1 (PfRbx1) and Skp1 (PfSkp1). PfCullin-1 and PfCullin-2 were predominantly expressed in erythrocytic trophozoite and schizont stages, with nucleocytoplasmic localization and chromatin association, suggesting their roles in different cellular compartments and DNA-associated processes. Immunoprecipitation, in vitro protein-protein interaction, and ubiquitination assay confirmed the presence of a functional Skp1-Cullin-1-Fbox (PfSCF) complex, comprising of PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein. Immunoprecipitation, sequence analysis, and ubiquitination assay indicated that PfCullin-2 forms a functional human CRL4-like complex (PfCRL4), consisting of PfRbx1, cleavage and polyadenylation specificity factor subunit_A and WD40 repeat proteins. PfCullin-2 knock-down at the protein level, which would hinder PfCRL4 assembly, significantly decreased asexual and sexual erythrocytic stage development. The protein levels of several pathways, including protein translation and folding, lipid biosynthesis and transport, DNA replication, and protein degradation were significantly altered upon PfCullin-2 depletion, which likely reflects association of PfCRL4 with multiple pathways. PfCullin-2-depleted schizonts had poorly delimited merozoites and internal membraned structures, suggesting a role of PfCRL4 in maintaining membrane integrity. PfCullin-2-depleted parasites had a significantly lower number of nuclei/parasite than the normal parasites, indicating a crucial role of PfCRL4 in cell division. We demonstrate the presence of functional CRLs in P. falciparum, with crucial roles for PfCRL4 in cell division and maintaining membrane integrity.
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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.