Mitotic activation of the kinase Aurora-A requires its binding partner Bora

Andrea Hutterer1, Daniela Berdnik2,3, Alex Schleiffer2, Juergen A. Knoblich1. 1) Institute of Molecular Biotechnology (IMBA), Vienna, Austria; 2) Institute of Molecular Pathology (IMP), Vienna, Austria; 3) Department of Biological Sciences, Stanford University, Stanford, CA.

During asymmetric cell division of precursor cells of the Drosophila peripheral nervous system the protein Numb is segregated into only one of the two daughter cells where it induces a particular developmental fate. Asymmetric Numb localization as well as centrosome maturation require the activity of the mitotic kinase Aurora-A. How Aurora-A is activated at the onset of mitosis is not clear yet.

In a screen for genes involved in asymmetric cell division we have identified the novel gene borealis (bora). bora mutants have identical phenotypes to auroraA mutants. Numb fails to localize asymmetrically and centrosome maturation is impaired. Genetic and biochemical experiments show a close functional connection between Bora and Aurora-A. Overexpression of bora can rescue the defects caused by mutations in auroraA. Bora is conserved in vertebrates and both Drosophila and human Bora can bind to Aurora-A and activate the kinase in vitro. Bora shows a striking subcellular localization: In interphase cells, Bora is a nuclear protein but upon entry into mitosis, Bora is excluded from the nucleus and translocates into the cytoplasm in a Cdc2 dependent manner. Additionally Cdc2 can phosphorylate Bora in vitro.

We propose a model in which activation of Cdc2 initiates the release of Bora into the cytoplasm where it can bind to and activate Aurora-A.

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