A protein interaction network of the malaria parasite Plasmodium falciparum

LaCount, Douglas; Vignali, Marissa; Chettier, Rakesh; Phansalkar, Amit; Bell, Russell; Hesselberth, Jay R.; Schoenfeld, Lori W.; Ota, Irene M.; Sahasrabudhe, Sudhir; Kurschner, Cornelia; Fields, Stanley; Hughes, Robert E.

doi:10.1038/nature04104

Cited by 465 publications

(448 citation statements)

References 30 publications

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“…Interestingly, the P. falciparum AP2 protein, PF14_0633, has been shown to form a homodimer upon binding to DNA (18), although in this case dimer formation is probably mediated by disulfide bonds rather than phosphorylation. Yeast two-hybrid screening has also highlighted the potential for heterodimer formation between other AP2s of P. falciparum (24). Western blot analysis of TgAP2XI-5 consistently detected two protein bands of 100 and 150 kDa, suggesting the possible presence of a heterodimer.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma Transcription Factor TgAP2XI-5 Regulates the Expression of Genes Involved in Parasite Virulence and Host Invasion

Walker

Gissot

Huot

et al. 2013

Journal of Biological Chemistry

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Background: Gene regulation in apicomplexan parasites is poorly understood. Results: The plant-like nuclear factor TgAP2XI-5 is targeted at gene promoters, including those required for parasite virulence. Conclusion: TgAP2XI-5 is a novel DNA sequence-specific transcription factor of T. gondii. Significance: Identifying master regulators of virulence gene expression is crucial for understanding of pathogenicity of this pathogen.

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Section: Discussionmentioning

confidence: 99%

Toxoplasma Transcription Factor TgAP2XI-5 Regulates the Expression of Genes Involved in Parasite Virulence and Host Invasion

Walker

Gissot

Huot

et al. 2013

Journal of Biological Chemistry

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“…Interestingly, yeast two-hybrid interaction data (36) show that HMGB2 is in the center of a broader network of proteins potentially involved in transcription regulation, including three AP2 domain plant-like transcription factors (supplemental Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

High Mobility Group Protein HMGB2 Is a Critical Regulator of Plasmodium Oocyst Development

Gissot

Ting

Daly

et al. 2008

Journal of Biological Chemistry

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The sexual cycle of Plasmodium is required for transmission of malaria from mosquitoes to mammals, but how parasites induce the expression of genes required for the sexual stages is not known. We disrupted the Plasmodium yoelii gene encoding high mobility group nuclear factor hmgb2, which encodes a DNA-binding protein potentially implicated in transcriptional regulation of malaria gene expression. We investigated its function in vivo in the vertebrate and invertebrate hosts. ⌬pyhmgb2 parasites develop into gametocytes but have drastic impairment of oocyst formation. A global transcriptome analysis of the ⌬pyhmgb2 parasites identified ϳ30 genes whose expression is down-regulated in the ⌬pyhmgb2 parasites. These genes are conserved in all malaria species, and more than 90% of these genes show a peak of mRNA expression at the gametocyte stage. Surprisingly, the transcripts coding for the Plasmodium berghei orthologues of those genes are stored and translated in the ookinete stage. Therefore, sexual stage protein expression appears to be both transcriptionally and translationally regulated with Plasmodium HMGB2 acting as an important regulator of malaria sexual stage gene expression.Plasmodium species, the causative agents of malaria, are the most deadly members of the apicomplexan phylum. As with other members of the Apicomplexa, Plasmodium has a multifaceted life cycle encompassing an asexual phase within the intermediate host and a sexual cycle in the mosquito. Gametocytogenesis and gametogenesis consist of an ensemble of processes leading to the differentiation of erythrocytic forms of the parasite into male or female gametocytes. These complex and coordinated steps ensure the transmission of the parasite to the invertebrate host and are required for transmission of malaria to mammalian hosts. Gametocytes form in mammalian host, are taken up by the mosquito during a blood meal, transform into gametes in the mosquito midgut, and then fuse to form a zygote. Zygotes differentiate into ookinetes that penetrate the midgut wall and differentiate into oocysts, in which sporozoites will develop.Starting from the well controlled vertebrate milieu, the parasite must adapt to the mosquito environment where temperature fluctuates and nutrients are limited. Gametocytogenesis requires growth arrest and a differentiation step that will prepare the parasite for these changes. Sexual differentiation is accompanied by a tightly controlled gene expression program during which ϳ200 -300 mRNAs are specifically expressed or predominantly expressed in sexual forms of the parasite (1-4). Transcriptional control of gene expression is implicated as a crucial step during this process with sex-specific transcript expression in gametocytes controlled by the sequences in the 5Ј-flanking regions (5).For some sexual stage genes post-translational processes mediate gene expression. The genes coding for P25 and P28 ookinete proteins (PY00522 and PY00523, respectively) are transcribed at the gametocyte stage, but their translation is delayed unti...

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“…These PPI networks correspond to Archaeglobus fulgidus (Motz et al, 2002), Kaposi sarcoma-associated herpes virus (KSHV) (Uetz et al, 2006), varicella-zoster virus (VZV) (Uetz et al, 2006), Bacillus subtilis (Noirot and NoirotGros, 2004;Hoebeke et al, 2001), Escherichia coli (Butland et al, 2005)), malaria parasite Plasmodium falciparum (LaCount et al, 2005), the worm Caenohabditis elegans (Li et al, 2004),…”

Section: Study Of Protein-protein Interaction Networkmentioning

confidence: 99%

Generalized walks-based centrality measures for complex biological networks

Estrada

2010

Journal of Theoretical Biology

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A strategy for zooming in and out the topological environment of a node in a complex network is developed. This approach is applied here to generalize the subgraph centrality of nodes in complex networks. In this case the zooming in strategy is based on the use of some known matrix functions which allow focusing locally on the environment of a node. When a zooming out strategy is applied new matrix functions are introduced, which give a more global picture of the topological surrounds of a node. These indices permit a modulation of the scales at which the environment of a node influences its centrality. We apply them to the study of 10 protein-protein interaction (PPI) networks. We illustrate the similarities and differences between the generalized subgraph centrality indices as well as among them and some classical centrality measures. We show here that the use of centrality indices based on the zooming in strategy identifies a larger number of essential proteins in the yeast PPI network than any of the other centrality measures studied.

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A protein interaction network of the malaria parasite Plasmodium falciparum

Cited by 465 publications

References 30 publications

Toxoplasma Transcription Factor TgAP2XI-5 Regulates the Expression of Genes Involved in Parasite Virulence and Host Invasion

Toxoplasma Transcription Factor TgAP2XI-5 Regulates the Expression of Genes Involved in Parasite Virulence and Host Invasion

High Mobility Group Protein HMGB2 Is a Critical Regulator of Plasmodium Oocyst Development

Generalized walks-based centrality measures for complex biological networks

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