ArticleThe Journal of biological chemistry2015
Deoxyhypusine Modification of Eukaryotic Translation Initiation Factor 5A (eIF5A) Is Essential for Trypanosoma brucei Growth and for Expression of Polyprolyl-containing Proteins.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- A gene therapy strategy for Deoxyhypusine Synthase (DHPS) syndrome.Research square · 2026Article
- Domain function and predicted structure of three heterodimeric endonuclease subunits of RNA editing catalytic complexes in Trypanosoma brucei.Nucleic acids research · 2022Article
- Role of eIF5A in Mitochondrial Function.International journal of molecular sciences · 2022Review
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Proteomics analysis reveals that the proto-oncogene eIF-5A indirectly influences the growth, invasion and replication of Toxoplasma gondii tachyzoite.Parasites & vectors · 2021Article
- Structural features and development of an assay platform of the parasite target deoxyhypusine synthase of Brugia malayi and Leishmania major.PLoS neglected tropical diseases · 2020Article
- Klf5 down-regulation induces vascular senescence through eIF5a depletion and mitochondrial fission.PLoS biology · 2020Article
- Editosome RNase III domain interactions are essential for editing and differ between life cycle stages inRNA (New York, N.Y.) · 2019Article
- Hypusine, a polyamine-derived amino acid critical for eukaryotic translation.The Journal of biological chemistry · 2018Review
- Polyamines in protozoan pathogens.The Journal of biological chemistry · 2018Review
- Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site Complementation between Pseudoenzyme Paralogs.Structure (London, England : 1993) · 2018Article
- A dual regulatory circuit consisting of S-adenosylmethionine decarboxylase protein and its reaction product controls expression of the paralogous activator prozyme in Trypanosoma brucei.PLoS pathogens · 2018Article
- Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations.Memorias do Instituto Oswaldo Cruz · 2018Article
- Ornithine uptake and the modulation of drug sensitivity inFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Evolutionary conserved role of eukaryotic translation factor eIF5A in the regulation of actin-nucleating formins.Scientific reports · 2017Article
- The Major Protein Arginine Methyltransferase inThe Journal of biological chemistry · 2017Article
- The Essential Role of Spermidine in Growth of Agrobacterium tumefaciens Is Determined by the 1,3-Diaminopropane Moiety.ACS chemical biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The eukaryotic protozoan parasite Trypanosoma brucei is the causative agent of human African trypanosomiasis. Polyamine biosynthesis is essential in T. brucei, and the polyamine spermidine is required for synthesis of a novel cofactor called trypanothione and for deoxyhypusine modification of eukaryotic translation initiation factor 5A (eIF5A). eIF5A promotes translation of proteins containing polyprolyl tracts in mammals and yeast. To evaluate the function of eIF5A in T. brucei, we used RNA interference (RNAi) to knock down eIF5A levels and found that it is essential for T. brucei growth. The RNAi-induced growth defect was complemented by expression of wild-type human eIF5A but not by a Lys-50 mutant that blocks modification by deoxyhypusine. Bioinformatics analysis showed that 15% of the T. brucei proteome contains 3 or more consecutive prolines and that actin-related proteins and cysteine proteases were highly enriched in the group. Steady-state protein levels of representative proteins containing 9 consecutive prolines that are involved in actin assembly (formin and CAP/Srv2p) were significantly reduced by knockdown of eIF5A. Several T. brucei polyprolyl proteins are involved in flagellar assembly. Knockdown of TbeIF5A led to abnormal cell morphologies and detached flagella, suggesting that eIF5A is important for translation of proteins needed for these processes. Potential specialized functions for eIF5A in T. brucei in translation of variable surface glycoproteins were also uncovered. Inhibitors of deoxyhypusination would be expected to cause a pleomorphic effect on multiple cell processes, suggesting that deoxyhypusine/hypusine biosynthesis could be a promising drug target in not just T. brucei but in other eukaryotic pathogens.
Indexed as
Identifiers
What OpenQuestion holds
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.