ArticleBMC molecular biology2008
Distinct and stage specific nuclear factors regulate the expression of falcipains, Plasmodium falciparum cysteine proteases.
Article in BMC molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 18 citations in OpenAlex.
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Chromatin Accessibility-Based Characterization of the Gene Regulatory Network Underlying Plasmodium falciparum Blood-Stage Development.Cell host & microbe · 2018Article
- Analysis of the spatial and temporal arrangement of transcripts over intergenic regions in the human malarial parasite Plasmodium falciparum.BMC genomics · 2013Article
- Centenary celebrations article: Cysteine proteases of human malaria parasites.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2011Article
- Analysis of the molecular mechanisms governing the stage-specific expression of a prototypical housekeeping gene during intraerythrocytic development of P. falciparum.Journal of molecular biology · 2011Article
- Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite.PLoS pathogens · 2010Article
- Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4.PLoS neglected tropical diseases · 2010Article
- Regulation of gene expression in protozoa parasites.Journal of biomedicine & biotechnology · 2010Review
- Patterns of gene-specific and total transcriptional activity during the Plasmodium falciparum intraerythrocytic developmental cycle.Eukaryotic cell · 2009Article
- Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva.BMC genomics · 2008Article
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3 authors at 1 institution in 1 country.
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Abstract
backgroundPlasmodium falciparum cysteine proteases (falcipains) play indispensable roles in parasite infection and development, especially in the process of host erythrocyte rupture/invasion and hemoglobin degradation. No detailed molecular analysis of transcriptional regulation of parasite proteases especially cysteine proteases has yet been reported. In this study, using a combination of transient transfection assays and electrophoretic mobility shift assays (EMSA), we demonstrate the presence of stage specific nuclear factors that bind to unique sequence elements in the 5'upstream regions of the falcipains and probably modulate the expression of cysteine proteases.
resultsFalcipains differ in their timing of expression and exhibit ability to compensate each other's functions at asexual blood stages of the parasite. Present study was undertaken to study the transcriptional regulation of falcipains. Transient transfection assay employing firefly luciferase as a reporter revealed that a ~1 kb sequence upstream of translational start site is sufficient for the functional transcriptional activity of falcipain-1 gene, while falcipain-2, -2' and -3 genes that exist within 12 kb stretch on chromosome 11 require ~2 kb upstream sequences for the expression of reporter luciferase activity. EMSA analysis elucidated binding of distinct nuclear factors to specific sequences within the 5'upstream regions of falcipain genes. Analysis of falcipains' 5'upstream regulatory regions did not reveal the presence of sequences known to bind general eukaryotic factors. However, we did find parasite specific sequence elements such as poly(dA) poly(dT) tracts, CCAAT boxes and a single 7 bp-G rich sequence, (A/G)NGGGG(C/A) in the 5' upstream regulatory regions of these genes, thereby suggesting the role(s) of Plasmodium specific transcriptional factors in the regulation of falcipain genes.
conclusionTaken together, these results suggest that expression of Plasmodium cysteine proteases is regulated at the transcriptional level and parasite specific factors regulate the expression of falcipain genes. These findings open new venues for further studies in identification of parasite specific transcription factors.
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