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J. Biol. Chem., Vol. 278, Issue 52, 52454-52460, December 26, 2003

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The Serine/Threonine Kinase Nek6 Is Required for Cell Cycle Progression through Mitosis^*

Min-Jean Yin, Lihua Shao, David Voehringer, Tod Smeal, and Bahija Jallal

From the SUGEN, Inc., South San Francisco, California 94080-4811

The Aspergillus nidulans protein NIMA (never in mitosis, gene A) is a protein kinase required for the initiation of mitosis, whereas its inactivation is necessary for mitotic exit. Here, we demonstrate that human NIMA-related kinase 6 (Nek6) is required for mitotic progression of human cells. Nek6 is phosphorylated and activated during M phase. Inhibition of Nek6 function by either overexpression of an inactive Nek6 mutant or elimination of endogenous Nek6 by siRNA arrests cells in M phase and triggers apoptosis. Time-lapse recording of the cell cycle progression of cells expressing kinase-inactive Nek6 reveals mitotic arrest at the metaphase stage prior to cells entering apoptosis. In contrast to NIMA and the closely related mammalian Nek2 kinase, which regulate centrosome function and separation, our data demonstrate an important function for Nek6 during mitosis and suggest that Nek6 kinase is required for metaphase-anaphase transition.

Received for publication, July 24, 2003 , and in revised form, October 8, 2003.

^* 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.

To whom correspondence should be addressed: 10724 Science Center Dr., San Diego, CA 92121. Tel.: 858-622-7438; Fax: 858-622-5999; E-mail: min-jean.yin{at}pfizer.com.

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