Studies on the Role of DIk/ZIP-Kinase in Mitosis and Cytokinesis

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Dlk, or more commonly termed ZIP kinase, plays a key role in regulation of cell motility, contractility, and mitosis, particularly cytokinesis. During mitosis, ZIP kinase associates with centrosomes, centromeres, the contractile ring and the midbody. Recent data revealed by mutant AC2NLS suggest that ZIP kinase plays a role in spindle assembly and in coordination of mitosis and cytokinesis and that these functions involve interaction with centromeres. In the following proposal we want to further elucidate the role of ZIP kinase at centromeres and the significance of centromere-specific H3T11 phosphorylation. We propose that ZIP kinase phosphorylates histone H3 at T11 and that this modification is either part of a centromere-specific histone code or that it is a signal for subsequent incorporation of CENP-A into chromatin. To proof these assumptions we want to 1} express mutant AC2NLS in an inducible fashion and follow its effects under synchronous conditions, 2) identify the interaction partners of ZIP kinase at mitotic structures, 3) establish inducible knockout systems 4) investigate chromosome-directed spindle assembly 5) investigate the role of H3T11 phosphorylation.