Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

The adenovirus E1A domains required for induction of DNA rereplication in G2/M arrested cells coincide with those required for apoptosis

Oncogene volume 18, pages 4767–4776 (1999)Cite this article

Abstract

Induction of apoptosis by adenovirus E1A in rodent cells is stimulated by wild type (wt) p53 but completely suppressed by mutated p53. The suppression is overcome by coexpression with Id proteins (Ids). The cells expressing E1A and Ids undergo apoptosis after accumulation in S phase, suggesting that S phase events are perturbed by E1A and Ids. The E1A domains required for induction of apoptosis, analysed by transfection with expression vectors for E1A, Ids and their mutants, followed by flow cytometry, reside in N-terminal (positions 17 – 38), CR1 and CR2 regions. Interaction of E1A with Ids requires the N-terminal and CR1 regions. The cyclin D1 promoter activity in S phase was reduced severely by E1A and this reduction is caused through CR1 and CR2 regions required for interaction with pRB. Analysis of DNA synthesis in G2/M arrested cells indicated that E1A is capable of inducing >4 N cells and this E1A-mediated DNA rereplication is enhanced by coexpression with Id-1H. The E1A domains required for induction of DNA rereplication coincide with those required for apoptosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW and Vogelstein B. . 1998 Science 282: 1497–1501.

  • Canman CE, Gilmer TM, Coutts SB and Kastan MB. . 1995 Genes Dev. 9: 600–611.

  • Chen C and Okayama H. . 1987 Mol. Cell. Biol. 7: 2745–2752.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Cox LS. . 1997 Trends Cell Biol. 7: 493–498.

  • Debbas M and White E. . 1993 Genes Dev. 7: 546–554.

  • Di Leonardo A, Khan SH, Linke SP, Greco V, Seidita G and Wahl GM. . 1997 Cancer Res. 57: 1013–1019.

  • Dyson N, Howley PM, Munger K and Harlow E. . 1989 Science 243: 934–987.

  • El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B. . 1993 Cell 75: 817–825.

  • Florio M, Hernandez MC, Yang H, Shu HK, Cleveland JL and Israel MA. . 1998 Mol. Cell. Biol. 18: 5435–5444.

  • Freeman RS, Estus S and Johnson EJ. . 1994 Neuron 12: 343–355.

  • Gunning P, Leavitt J, Muscat G, Ng S-Y and Kedes L. . 1987 Proc. Natl. Acad. Sci. USA 84: 4831–4835.

  • Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E and Cox LS. . 1995 Oncogene 10: 2427–2433.

  • Ishii T, Shimizu M, Kanayama Y, Nakada S, Nojima H and Oda K. . 1993 Exp. Cell Res. 208: 407–414.

  • Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B and Fornace Jr AJ. . 1992 Cell 71: 587–597.

  • Kimura G, Itagaki A and Summers J. . 1975 Int. J. Cancer 15: 694–706.

  • Kranenburg O, van der Eb Aj and Zantema A. . 1996 EMBO J. 15: 46–54.

  • Lahti JM, Li H and Kidd VJ. . 1997 J. Biol. Chem. 272: 10859–10869.

  • Lasorella A, Iavarone A and Israel MA. . 1996 Mol. Cell. Biol. 16: 2570–2578.

  • Lowe SW and Ruley HE. . 1993 Genes Dev. 7: 535–545.

  • Matsuoka S, Yamaguchi M and Matsukage A. . 1994 J. Biol. Chem. 269: 11030–11036.

  • Muller H, Lukas J, Schneider A, Warthoe P, Bartek J, Eilers M and Strauss M. . 1994 Proc. Natl. Acad. Sci. USA 91: 2945–2949.

  • Mymryk JS, Shire K and Bayley ST. . 1994 Oncogene 9: 1187–1193.

  • Nakajima T, Ohi N, Arai T, Nozaki N, Kikuchi A and Oda K. . 1995 Oncogene 10: 651–662.

  • Nakajima T, Yageta M, Shiotsu K, Morita K, Suzuki M, Tomooka Y and Oda K. . 1998 Proc. Natl. Acad. Sci. USA 95: 10590–10595.

  • Norton JD, Deed RW, Craggs G and Sablitzky F. . 1998 Trends Cell Biol. 8: 58–65.

  • Notterman D, Young S, Wainger B and Levine AJ. . 1998 Oncogene 17: 2743–2751.

  • Philipp A, Schneider A, Vasrik I, Finke K, Xiong Y, Beach D, Alitalo K and Eilers M. . 1994 Mol. Cell. Biol. 14: 4032–4043.

  • Prabhu S, Ignatova A, Park ST and Sun XH. . 1997 Mol. Cell. Biol. 17: 5888–5896.

  • Shikama N, Lyon J and La Thangue NB. . 1997 Trends Cell Biol. 7: 230–236.

  • Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM and Fornace Jr AJ. . 1994 Science 266: 1376–1380.

  • Sofer LY and Resnitzky D. . 1996 Oncogene 13: 2431–2437.

  • Tanaka K, Pracyk JB, Takeda K, Yu ZX, Ferrans VJ, Deshpande SS, Ozaki M, Hwang PM, Lowenstein CJ, Irani K and Finkel T. . 1998 J. Biol. Chem. 273: 25922–25928.

  • Tsunoda H, Terasawa T, Yageta M, Nakajima T, Tomooka Y, Tsuchida N and Oda K. . 1999 Biochem. Biophys. Res. Commun. 255: 722–730.

  • White E, Cipriani R, Sabbatini P and Denton A. . 1991 J. Virol. 65: 2968–2978.

  • Xiong Y, Zhang H and Beach D. . 1992 Cell 71: 505–514.

  • Xu J and Morris GF. . 1999 Mol. Cell. Biol. 19: 12–20.

  • Zhu L, van den Heuvel S, Helin K, Fattaey A, Ewen M, Livingston D, Dyson N and Harlow E. . 1993 Genes Dev. 7: 1111–1125.

Download references

Acknowledgements

We thank Dr E Harlow for the expression vectors for E1A mutants, NCdl, dl646N and dl922/947 and pCMVCD20, Dr M Kanzaki for pMEP4-CD20 and Drs S Kitazawa and G Peters for cyclin D1 promoter-luciferase constructs. This work is supported by special coordination funds of the Science and Technology Agency of the Japanese Government.

Author information

Authors and Affiliations

  1. Department of Biological Science and Technology, Science University of Tokyo, 2641 Yamazaki, Noda, 278, Japan

    Mika Yageta, Haruki Tsunoda, Toshinori Yamanaka, Yasuhiro Tomooka & Kinichiro Oda

  2. Department of Molecular Cellular Oncology and Microbiology, Faculty of Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113, Japan

    Takuma Nakajima & Nobuo Tsuchida

Authors
  1. Mika Yageta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haruki Tsunoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshinori Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takuma Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuhiro Tomooka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nobuo Tsuchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kinichiro Oda
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yageta, M., Tsunoda, H., Yamanaka, T. et al. The adenovirus E1A domains required for induction of DNA rereplication in G2/M arrested cells coincide with those required for apoptosis. Oncogene 18, 4767–4776 (1999). https://doi.org/10.1038/sj.onc.1203063

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203063

Keywords

This article is cited by

Search

Advanced search

Quick links