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.
Similar content being viewed by others
References
Imler, J. L., Schatz, C., Wasylyk, C., Chatton, B. & Wasylyk, B. Nature 332, 275–278 (1988).
Sistonen, L., Hölttä, E., Mäkelä, T. P., Keski-Oja, J. & Alitalo, K. EMBO J. 8, 815–822 (1989).
Schutte, J., Minna, J. D. & Birrer, M. J. Proc. natn. acad. Sci. U.S.A. 86, 2257–2261 (1989).
Hunter, T. Cell 64, 249–270 (1991).
Schneikert, J., Imler, J. L. & Wasylyk, B. Nucleic Acids Res. 19, 783–787 (1991).
Wasylyk, C., Flores, P., Gutman, A. & Wasylyk, B. EMBO J. 8, 3371–3378 (1989).
Gutman, A. & Wasylyk, B. Trends Genet. Sci. 7, 49–54 (1991).
Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. & Noda, M. Cell 56, 77–84 (1989).
Schutte, J. et al. Cell 59, 987–997 (1989).
Kane, S. E. & Gottesman, M. M. Cancer Biology 1, 127–136 (1990).
Ledwith, B. J., Manam, S., Kraynak, A. R., Nichols, W. W. & Bradley, M. O. Molec. cell. Biol. 10, 1545–1555 (1990).
Mercola, D., Westwick, J., Rundell, A. Y. K., Adamson, E. D. & Edwards, S. A. Gene 77, 253–265 (1988).
Riabowol, K. T., Vosatka, R. J., Ziff, E. B., Lamb, N. J. & Feramisco, J. R. Mol. Cell. Biol. 8, 1670–1676 (1988).
Schuermann, M. et al. Cell 56, 507–516 (1989).
Nakabeppu, Y. & Nathans, D. Cell (1991) 64, 751–759 (1991).
Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L. & Weitraub, H. Cell 61, 49–59 (1990).
Noda, M. et al. Proc. natn. Acad. Sci. U.S.A. 86, 162–166 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lloyd, A., Yancheva, N. & Wasylyk, B. Transformation suppressor activity of a Jun transcription factor lacking its activation domain. Nature 352, 635–638 (1991). https://doi.org/10.1038/352635a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/352635a0
- Springer Nature Limited
This article is cited by
-
Spontaneously evolved progenitor niches escape Yap oncogene addiction in advanced pancreatic ductal adenocarcinomas
Nature Communications (2023)
-
Selective antagonism of cJun for cancer therapy
Journal of Experimental & Clinical Cancer Research (2020)
-
FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer
Oncogene (2015)
-
The oncogene c-Jun impedes somatic cell reprogramming
Nature Cell Biology (2015)
-
Cellular processes of v-Src transformation revealed by gene profiling of primary cells - Implications for human cancer
BMC Cancer (2010)