ArticlePLoS neglected tropical diseases2014
LmaPA2G4, a homolog of human Ebp1, is an essential gene and inhibits cell proliferation in L. major.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- PA2G4 in health and disease: An underestimated multifunctional regulator.Journal of advanced research · 2025Review
- ErbB-3 BINDING PROTEIN 1 Regulates Translation and Counteracts RETINOBLASTOMA RELATED to Maintain the Root Meristem.Plant physiology · 2020Article
- Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway.Infection and immunity · 2017Article
- A mitochondrial HSP70 (HSPA9B) is linked to miltefosine resistance and stress response in Leishmania donovani.Parasites & vectors · 2016Article
- Enzyme Activity Assays for Protein Kinases: Strategies to Identify Active Substrates.Current drug discovery technologies · 2016Review
- The past, present, and future of Leishmania genomics and transcriptomics.Trends in parasitology · 2015Review
- Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase.PLoS neglected tropical diseases · 2015Article
- Fitness and Phenotypic Characterization of Miltefosine-Resistant Leishmania major.PLoS neglected tropical diseases · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have identified LmaPA2G4, a homolog of the human proliferation-associated 2G4 protein (also termed Ebp1), in a phosphoproteomic screening. Multiple sequence alignment and cluster analysis revealed that LmaPA2G4 is a non-peptidase member of the M24 family of metallopeptidases. This pseudoenzyme is structurally related to methionine aminopeptidases. A null mutant system based on negative selection allowed us to demonstrate that LmaPA2G4 is an essential gene in Leishmania major. Over-expression of LmaPA2G4 did not alter cell morphology or the ability to differentiate into metacyclic and amastigote stages. Interestingly, the over-expression affected cell proliferation and virulence in mouse footpad analysis. LmaPA2G4 binds a synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I∶C)] as shown in an electrophoretic mobility shift assay (EMSA). Quantitative proteomics revealed that the over-expression of LmaPA2G4 led to accumulation of factors involved in translation initiation and elongation. Significantly, we found a strong reduction of de novo protein biosynthesis in transgenic parasites using a non-radioactive metabolic labeling assay. In conclusion, LmaPA2G4 is an essential gene and is potentially implicated in fundamental biological mechanisms, such as translation, making it an attractive target for therapeutic intervention.
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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.