Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation.
Aurora-B, previously known as AIM-1, is a conserved eukaryotic mitotic protein kinase. In mammals, this kinase plays an essential role in chromosomal segregation processes, including chromosome condensation, alignment, control of spindle checkpoints, chromosome segregation, and cytokinesis. Aurora-B is overexpressed in various cancer cells, suggesting that the kinase activity perturbs chromosomal segregation processes. Its forced overexpression induces chromosomal number instability and progressive tumorigenicity in rodent cells in vitro and in vivo. Nevertheless, based on focus formation in BALB/c 3T3 A31-1-1 cells, Aurora-B is not oncogenic. Here, we show that Aurora-B kinase activity augments Ras-mediated cell transformation. RNA interference with short hairpin RNA inhibits transformation by Ras and its upstream oncogene Src, but not by the downstream oncogene Raf. In addition, the inner centromere protein, which is a passenger protein associated with Aurora-B, has a similar ability to potentiate the activity of oncogenic Ras. These data indicate that elevated Aurora-B activity promotes transformation by oncogenic Ras by enhancing oncogenic signaling and by converting chromosome number-stable cells to aneuploid cells.
Kanda
Akifumi
A
Department of Molecular Radiobiology, Division of Genome Biology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan.
Kawai
Hidehiko
H
Suto
Shiho
S
Kitajima
Shojiro
S
Sato
Sunao
S
Takata
Takashi
T
Tatsuka
Masaaki
M
D000782:Aneuploidy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D064107:Aurora Kinase B; D064127:Aurora Kinases; D041702:BALB 3T3 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D011905:Genes, ras / Q000502:physiology*; D016391:Genes, src / Q000502:physiology; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D048490:raf Kinases / Q000502:physiology
D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; C513185:Incenp protein, mouse; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D048490:raf Kinases; D015739:Nocodazole