Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells.
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.
Sasai
Kaori
K
Department of Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Katayama
Hiroshi
H
Stenoien
David L
DL
Fujii
Satoshi
S
Honda
Reiko
R
Kimura
Masashi
M
Okano
Yukio
Y
Tatsuka
Masaaki
M
Suzuki
Fumio
F
Nigg
Erich A
EA
Earnshaw
William C
WC
Brinkley
William R
WR
Sen
Subrata
S
D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D002503:Centromere / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002877:Chromosomes, Human; D005347:Fibroblasts / Q000201:enzymology*; D016195:G2 Phase / Q000235:genetics / Q000502:physiology; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases