Sphingosine-1-phosphate regulates Plasmodium histone deacetylase activity and exhibits epigenetic control over cell death and differentiation
singh, s.; Sah, R. K.; Anand, S.; Kumari, G.; Saini, M.; Hada, R. S.; Madan, E.; Gupta, A.
Show abstract
Histone deacetylases (HDACs) play a key role in cellular processes by the regulation of gene transcription. This study contributes a novel insight how Plasmodium falciparum HDAC (PfHDAC-1) is regulated by S1P produced by host erythrocyte SphK-1. The binding of S1P with endogenous nuclear extract PfHDAC-1 and recombinant PfHDAC-1 blocks their activity. A significant modulation in transcriptional regulation of P. falciparum HDAC regulated genes resulted upon inhibition of S1P production through blocking of hSphK-1 by clinical SphK-1 inhibitor PF-543. PF-543 led to profound decrease in S1P in the parasites nuclear fraction. The significant modulation of PfHDAC-1 regulated specific candidate genes related to gametocytogenesis, virulence and proliferation was observed in parasite treated with SphK-1 inhibitor, suggesting S1P targets PfHDAC-1 and participates in epigenetic regulation of these key cellular processes. The epigenetic modulation of parasite cell growth and differentiation by host provides a novel approach for the developmenthost-targeted therapeutics.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Beyond the MEP Pathway: a novel kinase required for prenol utilization by malaria parasites 95%
- Highly accurate protein structure prediction-based virtual docking pipeline accelerating the identification of anti-schistosomal compounds 95%
- The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection 94%
Similar papers in this journal
- Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion 95%
- A novel lipase with dual localisation in Trypanosoma brucei 94%
- Sodium Diethyldithiocarbamate antiparasitic activity against different Trypanosoma cruzi strains: Insights of its biological activity 94%
Similar papers in this journal
- Plasmodium falciparum Acetyl-CoA Synthetase is essential for parasite intraerythrocytic development and chromatin modification 96%
- Essential bromodomain TcBDF2 as a drug target against Chagas disease 95%
- Accelerating antimalarial drug discovery with a new high-throughput screen for fast-killing compounds 94%
Similar papers in this journal
- Protein SUMOylation is crucial for phagocytosis in Entamoeba histolytica trophozoites 93%
- Identification of ATP2B4 regulatory element containing functional genetic variants associated with severe malaria 93%
- Trypanosoma brucei J protein 2 functionally cooperates with the cytosolic Hsp70.4 and Hsp70 proteins 91%
Similar papers in this journal
- Targeting Leishmania donovani Sphingosine Kinase 1 using PF-543 enhances immune response and limits parasite load 95%
- The repositioning of epigenetic probes/inhibitors identifies new anti-schistosomal lead compounds and chemotherapeutic targets 95%
- Comparative clinical transcriptome of pir genes in severe Plasmodium vivax malaria 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.