Leila Equinet

Publications (4)9.81 Total impact

• Source

  Available from: Karine G Le Roch

  Article: A Plasmodium falciparum transcriptional cyclin-dependent kinase-related kinase with a crucial role in parasite proliferation associates with histone deacetylase activity.

  Jean Halbert, Lawrence Ayong, Leila Equinet, Karine Le Roch, Mary Hardy, Dean Goldring, Luc Reininger, Norman Waters, Debopam Chakrabarti, Christian Doerig
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  ABSTRACT: Cyclin-dependent protein kinases (CDKs) are key regulators of the eukaryotic cell cycle and of the eukaryotic transcription machinery. Here we report the characterization of Pfcrk-3 (Plasmodium falciparum CDK-related kinase 3; PlasmoDB identifier PFD0740w), an unusually large CDK-related protein whose kinase domain displays maximal homology to those CDKs which, in other eukaryotes, are involved in the control of transcription. The closest enzyme in Saccharomyces cerevisiae is BUR1 (bypass upstream activating sequence requirement 1), known to control gene expression through interaction with chromatin modification enzymes. Consistent with this, immunofluorescence data show that Pfcrk-3 colocalizes with histones. We show that recombinant Pfcrk-3 associates with histone H1 kinase activity in parasite extracts and that this association is detectable even if the catalytic domain of Pfcrk-3 is rendered inactive by site-directed mutagenesis, indicating that Pfcrk-3 is part of a complex that includes other protein kinases. Immunoprecipitates obtained from extracts of transgenic parasites expressing hemagglutinin (HA)-tagged Pfcrk-3 by using an anti-HA antibody displayed both protein kinase and histone deacetylase activities. Reverse genetics data show that the pfcrk-3 locus can be targeted only if the genetic modification does not cause a loss of function. Taken together, our data strongly suggest that Pfcrk-3 fulfils a crucial role in the intraerythrocytic development of P. falciparum, presumably through chromatin modification-dependent regulation of gene expression.
  Eukaryotic Cell 03/2010; 9(6):952-9. · 3.60 Impact Factor
• Article: The genes encoding cAMP-dependent protein kinase catalytic subunit homologues of the microsporidia Encephalitozoon intestinalis and E. cuniculi: molecular characterisation and phylogenetic analysis.

  Leila Equinet, Eric Bapteste, Marc Thellier, Meryem Ouarzane-Amara, Christian P Vivarès, Isabelle Desportes-Livage, Christian Doerig
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  ABSTRACT: A gene encoding a protein kinase was identified by homology-based PCR amplification in Encephalitozoon intestinalis, a microsporidian parasite pathogenic to humans, and its orthologue has been identified by database mining in the genome of the related species E. cuniculi, whose sequence has been recently published. Phylogenetic analysis revealed that the proteins encoded by these genes are homologues of the cAMP-dependent protein kinase catalytic subunits (PKAc). Southern blot analysis indicated that the EiPKAc gene is present in two copies in the E. intestinalis genome, whereas the E. cuniculi orthologue (EcPKAc) is a single copy gene. RT-PCR data showed that the EiPKAc gene is expressed in at least one of the intracellular stages during infection of the mammalian host cell by E. intestinalis.
  Parasitology International 01/2005; 53(4):277-85. · 2.13 Impact Factor
• Source

  Available from: PubMed Central

  Article: Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote.

  Pauline Ward, Leila Equinet, Jeremy Packer, Christian Doerig
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  ABSTRACT: Malaria, caused by the parasitic protist Plasmodium falciparum, represents a major public health problem in the developing world. The P. falciparum genome has been sequenced, which provides new opportunities for the identification of novel drug targets. Eukaryotic protein kinases (ePKs) form a large family of enzymes with crucial roles in most cellular processes; hence malarial ePKS represent potential drug targets. We report an exhaustive analysis of the P. falciparum genomic database (PlasmoDB) aimed at identifying and classifying all ePKs in this organism. Using a variety of bioinformatics tools, we identified 65 malarial ePK sequences and constructed a phylogenetic tree to position these sequences relative to the seven established ePK groups. Predominant features of the tree were: (i) that several malarial sequences did not cluster within any of the known ePK groups; (ii) that the CMGC group, whose members are usually involved in the control of cell proliferation, had the highest number of malarial ePKs; and (iii) that no malarial ePK clustered with the tyrosine kinase (TyrK) or STE groups, pointing to the absence of three-component MAPK modules in the parasite. A novel family of 20 ePK-related sequences was identified and called FIKK, on the basis of a conserved amino acid motif. The FIKK family seems restricted to Apicomplexa, with 20 members in P. falciparum and just one member in some other Apicomplexan species. The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the kinome of malaria parasites and that of yeast or mammalian cells.
  BMC Genomics 11/2004; 5:79. · 4.07 Impact Factor
• Article: Studies on the kinome of Plasmodium falciparum and biochemical characterization of atypical protein kinases /

  Leila. Equinet
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  ABSTRACT: Thesis (Ph.D.) -- University of Glasgow, 2004. Includes bibliographical references.