Cell cycle control in Plasmodium falciparum: a genomics perspective
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The molecular mechanisms regulating cell proliferation and development in malaria parasites are still largely unknown. Phenomenological observations, pertaining to the organisation of the cell cycle during schizogony or to the signal transduction pathways whose activation is responsible for the developmental stage transitions, can now be complemented with information gathered from genomic databases. The PlasmoDB database has been used extensively to identify putative homologues of a number of eukaryotic cell cycle regulators such as cyclins, cyclin-dependent kinases, factors involved in the control of DNA synthesis, and components of signal transduction pathways. However, gene identification based on sequence homology is limited by the fact that any Plasmodium-specific functional homologue will be missed by this approach. Furthermore, experimental data indicate that the structure of some regulatory pathways (unlike that of metabolic pathways) cannot be deducted directly from database mining. Because of these limitations in the direct exploitation of genomic database, elucidation of the organisation of the signal transduction and cell cycle machineries requires experimental, proteomics-based approaches such as the characterisation of protein complexes containing cell cycle regulators and the establishment of a map of protein-protein interactions involving these elements