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

Cell Motil Cytoskeleton. 2004 Dec;59(4):249-63. doi: 10.1002/cm.20039.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Cell Division / genetics
  • Cell Division / physiology*
  • Centromere / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Human*
  • Fibroblasts / enzymology*
  • G2 Phase / genetics
  • G2 Phase / physiology
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tumor Cells, Cultured

Substances

  • Chromosomal Proteins, Non-Histone
  • INCENP protein, human
  • RNA, Small Interfering
  • Recombinant Proteins
  • AURKB protein, human
  • AURKC protein, human
  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases