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MitoCheck: Regulation of mitosis by phosphorylation - a combined functional genomics, proteomics and chemical biology approach
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Eukaryotic cells pass their genomes from one cell generation to the next by first duplicating their DNA in S-phase and then segregating it into two separate copies during mitosis. The latter is an immensely complex process that remains poorly understood at the molecular level. Mistakes during mitosis contribute to cancer whereas mistakes during meiosis are the leading cause of infertility and mental retardation. Although many proteins required for mitosis have been identified, the entire set of proteins that are needed for this process remains unknown. Among those proteins that are known to be required for mitosis the protein kinases Cdk1, Plk1 and Aurora kinases have been particularly well studied, but even in these cases the actual molecular functions of these enzymes remain largely unknown. The main objectives of the Integrated Project MitoCheck are therefore to identify all human proteins that are required for mitosis, and to understand how protein kinases regulate these proteins by phosphorylation.
More background
To achieve these goals, MitoCheck is using RNA interference (RNAi) screens to identify all proteins that are required for mitosis in human cells, affinity purification and mass spectrometry to identify protein complexes and mitosis-specific phosphorylation sites on these, and small molecule inhibitors to determine which protein kinase is required for the phosphorylation of which substrate. MitoCheck is furthermore establishing clinical assays to validate mitotic proteins as prognostic biomarkers for cancer therapy.
Work Packages
MitoCheck is the largest integrated research project on cell cycle control within the Sixth Framework of the
European Union. Eight and a half million Euro will be provided to this multi-national, multi-disciplinary project by the European Commission over four years (2004-2008). Leading scientists from eleven research institutes, universities and industry in Austria, Germany, UK, Italy and France with a wide range of expertise in molecular and cell biology, biochemistry, modern microscopy techniques, proteomics, bioinformatics and clinical pathology join forces to take on the challenge of unraveling the mystery of cell division.
Participants
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