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Science 319 (5862): 469-472

Copyright © 2008 by the American Association for the Advancement of Science

Centromeric Aurora-B Activation Requires TD-60, Microtubules, and Substrate Priming Phosphorylation

Sara E. Rosasco-Nitcher, Weijie Lan, Sepideh Khorasanizadeh, P. Todd Stukenberg*

Abstract: The chromosome passenger complex (CPC) controls chromosome congression, kinetochore-microtubule attachments, and spindle checkpoint signaling during mitosis. Aurora-B kinase is the catalytic subunit of the CPC. To understand how a single kinase can regulate such diverse events, we have investigated the activation of Aurora-B and describe two distinct activation mechanisms. First, Aurora-B activation in vitro requires two cofactors, telophase disc–60kD (TD-60) and microtubules. TD-60 is critical to localize both the CPC and Haspin kinase activity to centromeres and thus regulates Aurora-B at several levels. Second, Aurora-B substrates can inhibit kinase activation, and this is relieved by phosphorylation of these substrates by the centromeric kinases Plk1 and Haspin. These regulatory mechanisms suggest models for phosphorylation by Aurora-B of centromeric substrates at unaligned chromosomes and merotelic attachments.

Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA.

* To whom correspondence should be addressed. E-mail: pts7h{at}

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