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.

  • Short Report
  • Published:

The SV40 large T oncoprotein disrupts DNA-binding of the cell cycle-regulated transcriptional repressor CDF

Abstract

A hallmark of neoplastic transformation by DNA tumor viruses is the deregulation of cell cycle genes. At least in some genes, this deregulation appears to be due to the oncoprotein-mediated disruption of complexes between E2F and pocket proteins and the ensuing generation of transcriptionally active free E2F. In the present study, we have analysed the effect of the SV40 large T oncoprotein (SV-LT) on the function of a different cell cycle-regulated transcriptional repressor, CDF, which is the principal regulator of the cdc25C, cyclin A and cdc2 genes. As shown by genomic footprinting of sorted G1 and G2 cell populations, transformation by SV-LT completely abrogated protection of the CDF binding site (CDE-CHR) in the cdc25C promoter. In agreement with this observation, expression of the SV-LT in fibroblasts led to a dramatic up-regulation of the cdc25C promoter in cells synchronized in G0. These findings indicate that the oncoprotein-mediated dissociation of the CDF repressor protein from its cognate DNA-binding site is a major mechanism in virus-induced transcriptional deregulation.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Boyer SN, Wazer DE and Band V. . 1996 Cancer Res. 56: 4620–4624.

  • Buchou T, Kranenburg O, van DH, Roelen D, Zantema A, Hall FL and Van der EB A. . 1993 Oncogene 8: 1765–1773.

  • Chang, TH-T, Ray FA, Thompson DA and Schlegel R. . 1997 Oncogene 14: 2383–2393.

  • Chellappan S, Kraus VB, Kroger B, Munger K, Howley PM, Phelps WC and Nevins JR. . 1992 Proc. Natl. Acad. Sci. USA 89: 4549–4553.

  • Cheng S, Schmidt GD, Murant T, Broker TR and Chow LT. . 1995 Genes Dev. 9: 2335–2349.

  • Cormack BP, Valdiva RH and Falkow S. . 1996 Gene 173: 33–38.

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

  • Dyson N, Dembski M, Fattaey A, Ngwu C, Ewen M and Helin K. . 1993 J. Virol. 67: 7641–7647.

  • Dyson N, Howley PM, Munger K and Harlow E. . 1989 Science 253: 934–937.

  • Jones DL and Munger K. . 1997 J. Virol. 71: 2905–2912.

  • Liu N, Lucibello FC, Körner K, Wolfraim LA, Zwicker J and Müller R. . 1997 Nucl. Acids Res. 24: 4915–4920.

  • Lucibello FC, Truss M, Zwicker J, Ehlert F, Beato M and Müller R. . 1995 EMBO J. 14: 132–142.

  • Nevins J.R. . 1992 Science 258: 424–429.

  • Oshima J, Steinmann KE, Campisi J and Schlegel R. . 1993 Oncogene 8: 2987–2993.

  • Schuermann M. . 1990 Nucl. Acids Res. 18: 4945–4946.

  • Schulze A, Zerfass K, Spitkovsky D, Middendorp S, Berges J, Helin K, Jansen-Dürr P and Henglein B. . 1995 Proc. Natl. Acad. Sci. USA 92: 11264–11268.

  • Spitkovsky D, Steiner P, Lukas J, Lees E, Pagano M, Schulze A, Joswig S, Picard D, Tommasino M, Eilers M and Jansen-Dürr P. . 1994 J. Virol. 68: 2206–2214.

  • Zwicker J, Gross C, Lucibello FC, Truss M, Ehlert F, Engeland K and Müller R. . 1995a Nucleic Acids Res. 23: 3822–3830.

  • Zwicker J, Lucibello FC, Wolfraim LA, Gross C, Truss M, Engeland K and Müller R. . 1995b EMBO J. 14: 4514–4522.

Download references

Acknowledgements

We are grateful to C Schalk for FACS analyses. This work was supported by grants from the DFG (SFB397 and Mu601/9) and the BMBF.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zwicker, J., Körner, K. & Müller, R. The SV40 large T oncoprotein disrupts DNA-binding of the cell cycle-regulated transcriptional repressor CDF. Oncogene 18, 2023–2025 (1999). https://doi.org/10.1038/sj.onc.1202063

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202063

Keywords

This article is cited by

Search

Quick links