Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells

Kaori Sasai, Hiroshi Katayama, David L. Stenoien, Satoshi Fujii, Reiko Honda, Masashi Kimura, Yukio Okano, Masaaki Tatsuka, Fumio Suzuki, Erich A. Nigg, William C. Earnshaw, William R. Brinkley, Subrata Sen

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

The function of Aurora-C kinase, a member of the Aurora kinase family identified in mammals, is currently unknown. We present evidence that Aurora-C, like Aurora-B kinase, is a chromosomal passenger protein localizing first to centromeres and then to the midzone of mitotic cells. Aurora-C transcript is expressed at a moderate level albeit about an order of magnitude lower than Aurora-B transcript in diploid human fibroblasts. The level of Aurora-C transcript is elevated in several human cancer cell types. Aurora-C and Aurora-B mRNA and protein expressions are maximally elevated during the G2/M phase but their expression profiles in synchronized cells reveal differential temporal regulation through the cell cycle with Aurora-C level peaking after that of Aurora-B during the later part of the M phase. Aurora-C, like Aurora-B, interacts with the inner centromere protein (INCENP) at the carboxyl terminal end spanning the conserved IN box domain. Competition binding assays and transfection experiments revealed that, compared with Aurora-C, Aurora-B has preferential binding affinity to INCENP and co-expression of the two in vivo interferes with INCENP binding, localization, and stability of these proteins. A kinase-dead mutant of Aurora-C had a dominant negative effect inducing multinucleation in a dose-dependent manner. siRNA mediated silencing of Aurora-C and Aurora-B also gave rise to multinucleated cells with the two kinases silenced at the same time displaying an additive effect. Finally, Aurora-C could rescue the Aurora-B silenced multinucleation phenotype, demonstrating that Aurora-C kinase function overlaps with and complements Aurora-B kinase function in mitosis.

Original languageEnglish
Pages (from-to)249-263
Number of pages15
JournalCell Motility and the Cytoskeleton
Volume59
Issue number4
DOIs
Publication statusPublished - Dec 1 2004
Externally publishedYes

Keywords

  • Aurora kinase
  • Centromere
  • Chromosomal passenger protein
  • Midzone
  • Mitosis

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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    Sasai, K., Katayama, H., Stenoien, D. L., Fujii, S., Honda, R., Kimura, M., Okano, Y., Tatsuka, M., Suzuki, F., Nigg, E. A., Earnshaw, W. C., Brinkley, W. R., & Sen, S. (2004). Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motility and the Cytoskeleton, 59(4), 249-263. https://doi.org/10.1002/cm.20039