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J. Biol. Chem., Vol. 283, Issue 19, 12763-12768, May 9, 2008

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Tousled-mediated Activation of Aurora B Kinase Does Not Require Tousled Kinase Activity in Vivo^*

Gary M. Riefler¹, Sharon Y. R. Dent^¶, and Jill M. Schumacher²

From the Departments of Molecular Genetics and ^¶Biochemistry and Molecular Biology, the Program in Genes & Development, and the Center of Excellence for Epigenetic Research, M. D. Anderson Cancer Center, University of Texas, Houston, Texas 77030

The Aurora kinases comprise an evolutionarily conserved protein family that is required for a variety of cell division events, including spindle assembly, chromosome segregation, and cytokinesis. Emerging evidence suggests that once phosphorylated, a subset of Aurora substrates can enhance Aurora kinase activity. Our previous work revealed that the Caenorhabditis elegans Tousled-like kinase TLK-1 is a substrate and activator of the AIR-2 Aurora B kinase in vitro and that partial loss of TLK-1 enhances the mitotic defects of an air-2 mutant. However, given that these experiments were performed in vitro and with partial loss of function alleles in vivo, a necessary step forward in our understanding of the relationship between the Aurora B and Tousled kinases is to prove that TLK-1 expression is sufficient for Aurora B activation in vivo. Here, we report that heterologous expression of wild-type and kinase-inactive forms of TLK-1 suppresses the lethality of temperature-sensitive mutants of the yeast Aurora B kinase Ipl1. Moreover, kinase-dead TLK-1 associates with and augments the activity of Ipl1 in vivo. Together, these results provide critical and compelling evidence that Tousled has a bona fide kinase-independent role in the activation of Aurora B kinases in vivo.

Received for publication, November 2, 2007 , and in revised form, March 6, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant R01 GM62181-06 (to J. M. S.) The work performed in the M. D. Anderson Cancer Center DNA facility was supported by NCI Grant CA-16672 from the National Institutes of Health. 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 supplemental Figs. 1 and 2 and references.

¹ Supported by Training Program in Biochemistry and Molecular Biology Grant T32 HD007325 21 and by Training Program in Molecular Genetics of Cancer Grant T32 CA009299 29.

² To whom correspondence should be addressed: Dept. of Molecular Genetics, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1006, Houston, TX 77030. Fax: 713-834-6339; E-mail: jschumac{at}mdanderson.org.