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J. Biol. Chem., Vol. 279, Issue 45, 47201-47211, November 5, 2004

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Direct Association with Inner Centromere Protein (INCENP) Activates the Novel Chromosomal Passenger Protein, Aurora-C^*

Xiangyu Li, Gyosuke Sakashita, Hideki Matsuzaki¶, Kenji Sugimoto||, Keiji Kimura**, Fumio Hanaoka**, Hisaaki Taniguchi¶, Koichi Furukawa, and Takeshi Urano

From the Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, ^¶Membrane Dynamics Project, Synchrotron Radiation Research Network, Harima Institute at Spring-8, RIKEN, Kouto, Mikazuki, Sayo, Hyogo 679-5148, ^||Division of Applied Biochemistry, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, Osaka 599-8531, ^**Cellular Physiology Laboratory, Discovery Research Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, and Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan

A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. The human Aurora paralogues Aurora-A, Aurora-B, and Aurora-C have a highly conserved catalytic domain. Extensive studies on the role of Aurora-A and Aurora-B have revealed distinct localizations and functions in regulating mitotic processes, whereas little is known about Aurora-C. The present study shows that human Aurora-C is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere protein (INCENP), which are known passenger proteins. We show that INCENP binds and activates Aurora-C in vivo and in vitro. Furthermore, Aurora-C co-expressed with INCENP elicits the phosphorylation of endogenous histone H3 in mammalian cells, even though this phosphorylation is not sufficient to establish chromosome condensation in interphase cells. We therefore suggest that Aurora-C is a novel chromosomal passenger protein that cooperates with Aurora-B to regulate mitotic chromosome dynamics in mammalian cells.

Received for publication, March 18, 2004 , and in revised form, August 12, 2004.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY714054 and AY714053.

^* This work was supported by a grant-in-aid for scientific research and the 21st Century COE Program from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Figs. S1 and S2 and Movies 1 and 2.

These two authors contributed equally to this work.

To whom correspondence should be addressed. 81-52-744-2071; Fax: 81-52744-2069; E-mail: turano{at}med.nagoya-u.ac.jp.

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