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Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation

Abstract

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.

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References

  • Adams RR, Eckley DM, Vagnarelli P, Wheatley SP, Gerloff DL, Mackay AM, Svingen PA, Kaufmann SH and Earnshaw WC . (2001a). Chromosoma, 110, 65–74.

  • Adams RR, Maiato H, Earnshaw WC and Carmena M . (2001b). J. Cell Biol., 153, 865–880.

  • Ambrosini G, Adida C and Altieri DC . (1997). Nat. Med., 3, 917–921.

  • Andrews PD, Knatko E, Moore WJ and Swedlow JR . (2003). Curr. Opin. Cell Biol., 15, 672–683.

  • Andrews PD, Ovechkina Y, Morrice N, Wagenbach M, Duncan K, Wordeman L and Swedlow JR . (2004). Dev. Cell, 6, 253–268.

  • Carmena M and Earnshaw WC . (2003). Nat. Rev. Mol. Cell. Biol., 4, 842–854.

  • Chen J, Jin S, Tahir SK, Zhang H, Liu X, Sarthy AV, McGonigal TP, Liu Z, Rosenberg SH and Ng SC . (2003). J. Biol. Chem., 278, 486–490.

  • Chen JG and Horwitz SB . (2002). Cancer Res., 62, 1935–1938.

  • Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N and Taylor SS . (2003). J. Cell Biol., 161, 267–280.

  • Fukuda S and Pelus LM . (2004). Biochem. Biophys. Res. Commun., 323, 636–644.

  • Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, Nigg EA, Gerloff DL and Earnshaw WC . (2004). J. Cell Biol., 166, 179–191.

  • Gigoux V, L'Hoste S, Raynaud F, Camonis J and Garbay C . (2002). J. Biol. Chem., 277, 23742–23746.

  • Goto H, Yasui Y, Kawajiri A, Nigg EA, Terada Y, Tatsuka M, Nagata K and Inagaki M . (2003). J. Biol. Chem., 278, 8526–8530.

  • Goto H, Yasui Y, Nigg EA and Inagaki M . (2002). Genes Cells, 7, 11–17.

  • Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL and Peters JM . (2003). J. Cell Biol., 161, 281–294.

  • Hei TK and Hall EJ . (1993). Cancer Res., 53, 1368–1372.

  • Honda R, Korner R and Nigg EA . (2003). Mol. Biol. Cell, 14, 3325–3341.

  • Hsu JY, Sun ZW, Li X, Reuben M, Tatchell K, Bishop DK, Grushcow JM, Brame CJ, Caldwell JA, Hunt DF, Lin R, Smith MM and Allis CD . (2000). Cell, 102, 279–291.

  • Kakunaga T and Crow JD . (1980). Science, 209, 505–507.

  • Kakunaga T and Yamasaki H . (eds). (1985). Transformation Assay of Established Cell Lines: Mechanisms and Application. Oxford University Press: London.

    Google Scholar 

  • Katayama H, Ota T, Jisaki F, Ueda Y, Tanaka T, Odashima S, Suzuki F, Terada Y and Tatsuka M . (1999). J. Natl. Cancer Inst., 91, 1160–1162.

  • Kawajiri A, Yasui Y, Goto H, Tatsuka M, Takahashi M, Nagata K and Inagaki M . (2003). Mol. Biol. Cell, 14, 1489–1500.

  • Kizaka S and Hakura A . (1989). Mol. Cell Biol., 9, 5669–5675.

  • Lampson MA, Renduchitala K, Khodjakov A and Kapoor TM . (2004). Nat. Cell Biol., 6, 232–237.

  • Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC and Altieri DC . (1998). Nature, 396, 580–584.

  • Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao YC, Deng X, Tatsuka M, Narumiya S, May Jr WS, Nosaka T, Semba K, Inoue T, Satoh T, Inagaki M and Kitamura T . (2003). Dev. Cell, 4, 549–560.

  • Murata-Hori M, Fumoto K, Fukuta Y, Iwasaki T, Kikuchi A, Tatsuka M and Hosoya H . (2000). J. Biochem. (Tokyo), 128, 903–907.

  • Murata-Hori M, Tatsuka M and Wang YL . (2002). Mol. Biol. Cell, 13, 1099–1108.

  • Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y and Tatsuka M . (2002). Cancer Res., 62, 5168–5177.

  • Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds Jr FH and Stephenson JR . (1983). Proc. Natl. Acad. Sci. USA, 80, 4218–4222.

  • Sampath SC, Ohi R, Leismann O, Salic A, Pozniakovski A and Funabiki H . (2004). Cell, 118, 187–202.

  • Sasai K, Katayama H, Stenoien DL, Fujii S, Honda R, Kimura M, Okano Y, Tatsuka M, Suzuki F, Nigg EA, Earnshaw WC, Brinkley WR and Sen S . (2004). Cell Motil. Cytoskelet., 59, 249–263.

  • Schumacher JM, Golden A and Donovan PJ . (1998). J. Cell Biol., 143, 1635–1646.

  • Shimizu T, Kato MV, Nikaido O and Suzuki F . (1995). Jpn. J. Cancer Res., 86, 546–554.

  • Sommer KW, Schamberger CJ, Schmidt GE, Sasgary S and Cerni C . (2003). Oncogene, 22, 4266–4280.

  • Tatsuka M . (2005). Signal Transduction of Cell Division. Miki T (ed). Research Signpost: Kerala, India.

    Google Scholar 

  • Tatsuka M, Katayama H, Ota T, Tanaka T, Odashima S, Suzuki F and Terada Y . (1998). Cancer Res., 58, 4811–4816.

  • Tatsuka M, Mitsui H, Wada M, Nagata A, Nojima H and Okayama H . (1992). Nature, 359, 333–336.

  • Tatsuka M, Ota T, Yamagishi N, Kashihara Y, Wada M, Matsuda N, Mitsui H, Seiki M and Odashima S . (1996). Mol. Carcinogen., 15, 300–308.

  • Tatsuka M, Sato S, Kitajima S, Suto S, Kawai H, Miyauchi M, Ogawa I, Maeda M, Ota T and Takata T . (2005). Oncogene, 24, 1122–1127.

  • Temme A, Diestelkoetter-Bachert P, Schmitz M, Morgenroth A, Weigle B, Rieger MA, Kiessling A and Rieber EP . (2005). Biochem. Biophys. Res. Commun., 327, 765–773.

  • Temme A, Rieger M, Reber F, Lindemann D, Weigle B, Diestelkoetter-Bachert P, Ehninger G, Tatsuka M, Terada Y and Rieber EP . (2003). Mol. Biol. Cell, 14, 78–92.

  • Terada Y . (2001). Cell Struct. Funct., 26, 653–657.

  • Terada Y, Tatsuka M, Suzuki F, Yasuda Y, Fujita S and Otsu M . (1998). EMBO J., 17, 667–676.

  • Tsutsui T, Maizumi H and Barrett JC . (1984). Carcinogenesis, 5, 89–93.

  • Urano T, Emkey R and Feig LA . (1996). EMBO J., 15, 810–816.

  • Wu JC, Chen TY, Yu CT, Tsai SJ, Hsu JM, Tang MJ, Chou CK, Lin WJ, Yuan CJ and Huang CY . (2005). J. Biol. Chem., 280, 9013–9022.

  • Yagi T, Sasayama S, Sasai H and Kakunaga T . (1989). Mol. Carcinog., 1, 222–228.

  • Yasui Y, Urano T, Kawajiri A, Nagata K, Tatsuka M, Saya H, Furukawa K, Takahashi T, Izawa I and Inagaki M . (2004). J. Biol. Chem., 279, 12997–13003.

  • Zeitlin SG, Shelby RD and Sullivan KF . (2001). J. Cell Biol., 155, 1147–1157.

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Correspondence to Masaaki Tatsuka.

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Kanda, A., Kawai, H., Suto, S. et al. Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation. Oncogene 24, 7266–7272 (2005). https://doi.org/10.1038/sj.onc.1208884

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  • DOI: https://doi.org/10.1038/sj.onc.1208884

Keywords

  • transformation susceptibility
  • Ras
  • Src
  • Raf
  • Aurora
  • kinase

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