Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation
| Autor: | Hidehiko Kawai, Akifumi Kanda, Masaaki Tatsuka, Sunao Sato, Shojiro Kitajima, Shiho Suto, Takashi Takata |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
BALB 3T3 Cells Chromosomal Proteins Non-Histone Aurora B kinase Antineoplastic Agents Protein Serine-Threonine Kinases Biology Mice Aurora Kinases Genetics Animals Aurora Kinase B c-Raf Kinase activity Protein kinase A Molecular Biology Mitosis Nocodazole Aneuploidy Molecular biology Cell biology Genes src Cell Transformation Neoplastic Genes ras RNA Interference raf Kinases Cytokinesis Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Oncogene. 24:7266-7272 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1208884 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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