Letter | Published:

Transformation suppressor activity of a Jun transcription factor lacking its activation domain

Naturevolume 352pages635638 (1991) | Download Citation

Subjects

Abstract

THE oncoprotein c-Jun is thought to be a mediator of ras transformation as both its synthesis and activity as a transcription factor are stimulated by ras expression1,2. But c-Jun co-operates with ras in transformation assays3, suggesting that they act along different pathways (reviewed in ref. 4). Here we show by means of a dominant-negative mutated transcription factor that c-Jun potentially in conjunction with other factors that interact with it is necessary for transformation by ras. The mutant Jun lacks an activation domain and blocks stimulation of transcription by several oncoproteins, including Ras, v-Src, polyoma middle T, c-Jun and c-Fos, as well as by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibition is specific for motifs that bind Jun: activation of an NF-κB/Rel motif is not affected. This Jun mutant acts as an anti-oncogene in ras-trans-formed cells, generating non-transformed revertants that have acquired anchorage and density-dependent growth, as well as reduced tumorigenicity in vivo. Mutants of other transcription factors designed to inhibit transformation will enable us to study their role in signal transduction.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Imler, J. L., Schatz, C., Wasylyk, C., Chatton, B. & Wasylyk, B. Nature 332, 275–278 (1988).

  2. 2

    Sistonen, L., Hölttä, E., Mäkelä, T. P., Keski-Oja, J. & Alitalo, K. EMBO J. 8, 815–822 (1989).

  3. 3

    Schutte, J., Minna, J. D. & Birrer, M. J. Proc. natn. acad. Sci. U.S.A. 86, 2257–2261 (1989).

  4. 4

    Hunter, T. Cell 64, 249–270 (1991).

  5. 5

    Schneikert, J., Imler, J. L. & Wasylyk, B. Nucleic Acids Res. 19, 783–787 (1991).

  6. 6

    Wasylyk, C., Flores, P., Gutman, A. & Wasylyk, B. EMBO J. 8, 3371–3378 (1989).

  7. 7

    Gutman, A. & Wasylyk, B. Trends Genet. Sci. 7, 49–54 (1991).

  8. 8

    Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. & Noda, M. Cell 56, 77–84 (1989).

  9. 9

    Schutte, J. et al. Cell 59, 987–997 (1989).

  10. 10

    Kane, S. E. & Gottesman, M. M. Cancer Biology 1, 127–136 (1990).

  11. 11

    Ledwith, B. J., Manam, S., Kraynak, A. R., Nichols, W. W. & Bradley, M. O. Molec. cell. Biol. 10, 1545–1555 (1990).

  12. 12

    Mercola, D., Westwick, J., Rundell, A. Y. K., Adamson, E. D. & Edwards, S. A. Gene 77, 253–265 (1988).

  13. 13

    Riabowol, K. T., Vosatka, R. J., Ziff, E. B., Lamb, N. J. & Feramisco, J. R. Mol. Cell. Biol. 8, 1670–1676 (1988).

  14. 14

    Schuermann, M. et al. Cell 56, 507–516 (1989).

  15. 15

    Nakabeppu, Y. & Nathans, D. Cell (1991) 64, 751–759 (1991).

  16. 16

    Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L. & Weitraub, H. Cell 61, 49–59 (1990).

  17. 17

    Noda, M. et al. Proc. natn. Acad. Sci. U.S.A. 86, 162–166 (1989).

Download references

Author information

Affiliations

  1. LGME-CNRS, U184-INSERM, Institut de Chimie Biologique, Faculté de Medecine, 11 rue Humann, 67085, Strasbourg Cedex, France

    • Alison Lloyd
    • , Nina Yancheva
    •  & Bohdan Wasylyk

Authors

  1. Search for Alison Lloyd in:

  2. Search for Nina Yancheva in:

  3. Search for Bohdan Wasylyk in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/352635a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.