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  • Original Paper
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Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16INK4a and Cdk2/Cyclin E complex activation

Oncogene volume 19, pages 3225–3234 (2000)Cite this article

Abstract

Survivin is observed uniquely in tumor cells and developmental cells, which undergo either inappropriate or programmed cell growth. In the current study, we investigated the influence of Survivin on cell cycle. Overexpression of Survivin resulted in accelerated S phase shift, resistance to G1 arrest, and activated Cdk2/Cyclin E complex leading Rb phosphorylation. In addition, nuclear translocation of Survivin followed by an interaction with Cdk4 was detected. Interestingly, Survivin nuclear translocation coincided with S phase shift, and prevention of nuclear transport suppressed Survivin nuclear translocation and S phase shift. Further, we also observed that Survivin competitively interacted with the Cdk4/p16INK4a complex in a cell free system and in vivo. These results suggest that Survivin initiates the cell cycle entry as a result of nuclear translocation followed by an interaction with Cdk4.

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References

  • Adida C, Berrebi D, Peuchmaur M, Reyes-Mugica M and Altieri DC. . 1998a Lancet 351: 882–883.

  • Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J and Altieri DC. . 1998b Am. J. Pathol. 152: 43–49.

  • Albrecht JH, Poon RY, Ahonen CL, Rieland BM, Deng C and Crary GS. . 1998 Oncogene 16: 2141–2150.

  • Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornbery NA, Wong WW and Yuan J. . 1996 Cell 87: 171.

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

  • Ambrosini G, Adida C, Sirugo G and Altieri DC. . 1998 J. Biol. Chem. 273: 11177–11182.

  • Buchkovich K, Duffy LA and Harlow E. . 1989 Cell 58: 1097–1105.

  • Buttyan R, Olson CA, Pintar J, Clang C, Bandky M, Ng P and Sawczuk I. . 1989 Mol. Cell. Biol. 9: 3473–3481.

  • Byeon IJ, Li J, Ericson K, Selby TL, Tevelev A, Kim HJ, O’Maille P and Tsai MD. . 1998 Mol. Cell. 1: 421–431.

  • Chen PL, Scully P, Shew JY, Wang JY and Lee WH. . 1989 Cell 58: 1193–1198.

  • Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM and Sherr CJ. . 1999 EMBO J. 18: 1572–1583.

  • Clem RJ and Miller LK. . 1994 Mol. Cell. Biol. 14: 5212–5222.

  • DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang CM and Livingston DM. . 1989 Cell 58: 1085–1095.

  • Deveraux QL, Takahashi R, Salvesen GS and Reed JC. . 1997 Nature 388: 300–304.

  • Duckett CS, Nava VE, Gedrich RW, Clem RJ, Dongen JLV, Gilfillan MC, Shiels H, Hardwick JM and Thompson CB. . 1996 EMBO J. 15: 2685–2694.

  • Gagliardini V, Fernandez PA, Lee RK, Drexler HC, Rotello RJ, Fishman MC and Yuan J. . 1994 Science 263: 826–828.

  • Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ. . 1993 Cell 75: 805–816.

  • Hirai H, Roussel MF, Kato JY, Ashmun RA and Sherr CJ. . 1995 Mol. Cell. Biol. 15: 2672–2681.

  • Ito T, Shiraki K, Sugimoto K, Yamanaka T, Fujikawa K, Ito M, Takase K, Moriyama M, Kawano H, Hayashida M, Nakano T and Suzuki A. . 2000 Hepatology 31: 1080–1085.

  • Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T and Tanigawa N. . 1998 Cancer Res. 58: 5071–5074.

  • LaCasse EC, Baird S, Korneluk RG and MacKenzie AE. . 1998 Oncogene 17: 3247–3259.

  • Li F and Altieri DC. . 1999 Cancer Res. 59: 3143–3151.

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

  • Li Y, Jenkins CW, Nichols MA and Xiong Y. . 1994 Oncogene 9: 2261–2268.

  • Lin BT, Gruenwald S, Morla AO, Lee WH and Wang JY. . 1991 EMBO J. 10: 857–864.

  • Lu CD, Altieri DC and Tanigawa N. . 1998 Cancer Res. 58: 1808–1812.

  • Miura M, Friedlander RM and Yuan J. . 1995 Proc. Natl. Acad. Sci. USA 92: 8318–8322.

  • Nagata S. . 1994 Phil. Trans. R. Soc. Lond. 345: 281–287.

  • Nagata S. . 1997 Cell 88: 355–365.

  • Nagata S and Golstein P. . 1995 Science 267: 1449–1456.

  • Parry D, Mahony D, Wills K and Lees E. . 1999 Mol. Cell. Biol. 19: 1775–1783.

  • Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P and Massague J. . 1994 Cell 78: 59–66.

  • Reynisdottir I and Massague J. . 1997 Genes Dev. 11: 492–503.

  • Sherr CJ and Roberts JM. . 1995 Genes Dev. 9: 1149–1163.

  • Sherr CJ and Roberts JM. . 1999 Genes Dev. 13: 1501–1512.

  • Stein GH, Drullinger LF, Soulard A and Dulic V. . 1999 Mol. Cell. Biol. 19: 2109–2117.

  • Sugimoto M, Nakamura T, Ohtani N, Hampson L, Hampson IN, Shimamoto A, Furuichi Y, Okumura K, Niwa S, Taya Y and Hara E. . 1999 Genes Dev. 13: 3027–3033.

  • Suzuki A, Enari M, Eguchi Y, Matsuzawa A, Nagata S, Tsujimoto Y and Iguchi T. . 1996 EMBO J. 15: 211–215.

  • Suzuki A, Ito T, Kawano H, Hayashida M, Hayasaki Y, Tsutomi Y, Akahane K, Nakano T, Miura M and Shiraki K. . 2000 Oncogene 19: 1346–1353.

  • Suzuki A, Tsutomi Y, Akahane K, Araki T and Miura M. . 1998 Oncogene 17: 931–940.

  • Suzuki A, Tsutomi Y, Miura M and Akahane K. . 1999a Oncogene 18: 1239–1244.

  • Suzuki A, Tsutomi Y, Yamamoto N, Shibutani T and Akahane K. . 1999b Mol. Cell. Biol. 19: 3842–3847.

  • Swana HS, Grossman D, Anthony JN, Weiss RM and Altieri DC. . 1999 N. Engl. J. Med. 341: 4522–453.

  • Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T and Reed JC. . 1998 Cancer Res. 58: 5315–5320.

  • Wyllie AH, Kerr JFR and Currie AR. . 1980 Int. Rev. Cytol. 68: 251–306.

  • Xue D and Horvitz HR. . 1995 Nature 377: 248–251.

  • Yonehara S, Ishii A and Yonehara M. . 1989 J. Exp. Med. 169: 1747–1756.

  • Zhu X, Ohtsubo M, Bohmer RM, Roberts JM and Associan RK. . 1996 J. Cell Biol. 133: 391–403.

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Acknowledgements

We thank Dr Yukiko Gotoh, University of Tokyo, for her valuable discussion. The preparation of this manuscript was supported by the Idest Inc., Edmond, OK, USA.

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Authors and Affiliations

  1. Project for the Cell Death Research, Basic Technology Research Laboratory, Daiichi Pharmaceutical Co, Ltd, Tokyo R&D Center, Kitakasai 1-16-13, Edogawa-ku, 134-8630, Tokyo, Japan

    Atsushi Suzuki, Midori Hayashida & Hirokazu Kawano

  2. The First Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, 514-8507, Mie, Japan

    Takeshi Ito, Takeshi Nakano & Katsuya Shiraki

  3. Department of Neuroanatomy, Biomedical Research Center, Osaka University Medical School, Yamadaoka 2-2, Suita, 565, Osaka, Japan

    Masayuki Miura

  4. New Product Research Laboratories IV, Daiichi Pharmaceutical Co, Ltd, Tokyo R&D Center, Kitakasai 1-16-13, Edogawa-ku, 134-8630, Tokyo, Japan

    Kouichi Akahane

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  1. Atsushi Suzuki
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Suzuki, A., Hayashida, M., Ito, T. et al. Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16INK4a and Cdk2/Cyclin E complex activation. Oncogene 19, 3225–3234 (2000). https://doi.org/10.1038/sj.onc.1203665

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