Fennell, C, Babbitt, S, Russo, I, Wilkes, J, Ranford-Cartwright, L, Goldberg, DE and Doerig, C (2009) PfeIK1, a eukaryotic initiation factor 2α kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation. Malaria Journal, 8 (1). 99 - 99. ISSN 1475-2875

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Background: Post-transcriptional control of gene expression is suspected to play an important role in malaria parasites. In yeast and metazoans, part of the stress response is mediated through phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), which results in the selective translation of mRNAs encoding stress-response proteins.

Methods: The impact of starvation on the phosphorylation state of PfeIF2α was examined. Bioinformatic methods were used to identify plasmodial eIF2α kinases. The activity of one of these, PfeIK1, was investigated using recombinant protein with non-physiological substrates and recombinant PfeIF2α. Reverse genetic techniques were used to disrupt the pfeik1 gene.

Results: The data demonstrate that the Plasmodium falciparum eIF2α orthologue is phosphorylated in response to starvation, and provide bioinformatic evidence for the presence of three eIF2α kinases in P. falciparum, only one of which (PfPK4) had been described previously. Evidence is provided that one of the novel eIF2α kinases, PfeIK1, is able to phosphorylate the P. falciparum
eIF2α orthologue in vitro. PfeIK1 is not required for asexual or sexual development of the parasite, as shown by the ability of pfeik1- parasites to develop into sporozoites. However, eIF2α phosphorylation in response to starvation is abolished in pfeik1- asexual parasites

Conclusion: This study strongly suggests that a mechanism for versatile regulation of translation by several kinases with a similar catalytic domain but distinct regulatory domains, is conserved in P. falciparum.

Item Type: Article
Additional Information: This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: Catalytic Domain Plasmodium Falciparum Asexual Parasite Amino Acid Starvation Asexual Cycle
Subjects: Q Science > QH Natural history
Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 09 Apr 2019 11:30
Last Modified: 15 Apr 2019 15:22
URI: https://eprints.keele.ac.uk/id/eprint/6171

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