ArticlePLoS pathogens2014
Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 204 citations in OpenAlex.
- Five-layer systems analysis ofeLife · 2026Article
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Voices of Eukaryotic Microbes: Chemical Communication Via Quorum Sensing.Microbial ecology · 2026Review
- Potent kinase inhibitors from the Merck KGaA OGHL: Novel hits against Trypanosoma brucei with potential for repurposing.PLoS neglected tropical diseases · 2025Article
- Fexinidazole results in specific effects on DNA synthesis and DNA damage in the African trypanosome.PLoS neglected tropical diseases · 2025Article
- Discovery of effectors for casein kinase signaling in the African trypanosome.Scientific reports · 2025Article
- A limitation lifted: A conditional knockdown system reveals essential roles for Polo-like kinase and Aurora kinase 1 inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Activity-based chemoproteomic profiling reveals the active kinome ofFrontiers in pharmacology · 2025Article
- TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.Scientific reports · 2024Article
- Aurora B controls anaphase onset and error-free chromosome segregation in trypanosomes.The Journal of cell biology · 2024Article
- Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes.Nature communications · 2024Article
- Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes.eLife · 2024Article
- Differentiation granules, a dynamic regulator of T. brucei development.Nature communications · 2024Article
- An unconventional regulatory circuitry involving Aurora B controls anaphase onset and error-free chromosome segregation in trypanosomes.bioRxiv : the preprint server for biology · 2024Article
- Immunoprecipitation of RNA-DNA hybrid interacting proteins in Trypanosoma brucei reveals conserved and novel activities, including in the control of surface antigen expression needed for immune evasion by antigenic variation.Nucleic acids research · 2023Article
- Characterisation of TbSmee1 suggests endocytosis allows surface-bound cargo to enter the trypanosome flagellar pocket.Journal of cell science · 2023Article
- Cell-cell communication in African trypanosomes.Microbiology (Reading, England) · 2023Review
- In vitro and in vivo evaluation of kinase and protease inhibitors against Trypanosoma evansi.Veterinary research communications · 2023Article
- ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum.Molecular biology of the cell · 2023Article
- Two cold shock domain containing proteins trigger the development of infectious Trypanosoma brucei.PLoS pathogens · 2023Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The African trypanosome, Trypanosoma brucei, maintains an integral link between cell cycle regulation and differentiation during its intricate life cycle. Whilst extensive changes in phosphorylation have been documented between the mammalian bloodstream form and the insect procyclic form, relatively little is known about the parasite's protein kinases (PKs) involved in the control of cellular proliferation and differentiation. To address this, a T. brucei kinome-wide RNAi cell line library was generated, allowing independent inducible knockdown of each of the parasite's 190 predicted protein kinases. Screening of this library using a cell viability assay identified ≥42 PKs that are required for normal bloodstream form proliferation in culture. A secondary screen identified 24 PKs whose RNAi-mediated depletion resulted in a variety of cell cycle defects including in G1/S, kinetoplast replication/segregation, mitosis and cytokinesis, 15 of which are novel cell cycle regulators. A further screen identified for the first time two PKs, named repressor of differentiation kinase (RDK1 and RDK2), depletion of which promoted bloodstream to procyclic form differentiation. RDK1 is a membrane-associated STE11-like PK, whilst RDK2 is a NEK PK that is essential for parasite proliferation. RDK1 acts in conjunction with the PTP1/PIP39 phosphatase cascade to block uncontrolled bloodstream to procyclic form differentiation, whilst RDK2 is a PK whose depletion efficiently induces differentiation in the absence of known triggers. Thus, the RNAi kinome library provides a valuable asset for functional analysis of cell signalling pathways in African trypanosomes as well as drug target identification and validation.
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