Abstract
A KEY event in the response of cells to proliferative signals is the rapid, transient induction of the c-fos proto-oncogene, which is mediated through the serum response element (SRE) in the fos promoter1–4. Genomic footprinting5,6 and transfection experi-ments7–9 suggest that this activation occurs through a ternary complex that includes the serum response factor (SRF)10 and the ternary complex factor p62 (ref. 7). Interaction of p62TCF with the SRF-SRE binary complex requires a CAGGA tract immediately upstream of the SRE (ref. 7). Proteins of the ets proto-oncogene family bind to similar sequences11–13and we have found that a member of this family, Elk-1 (ref. 14), forms SRF-dependent ternary complexes with the SRE. Elk-1 and p62TCF have the same DNA sequence requirements and antibodies against Elk-1 block the binding of both proteins. Furthermore, we show that like p62TCF, Elk-1 forms complexes with the yeast SRF-homologue MCM1 but not with yeast ARG80 (ref. 15). But ARG80 mutants that convey interaction with p62TCF can also form complexes with Elk-1. The similarity, or even identity, between Elk-1 and p62TCF suggests a novel regulatory role for Ets proteins that is effected through interaction with other proteins, such as SRF. Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control16.
References
Greenberg, M. E. & Ziff, E. B. Nature 311, 433–438 (1984).
Treisman, R. Cell 42, 889–902 (1985).
Gilman, M. Z., Wilson, R. N. & Weinberg, R. A. Molec. cell. Biol. 6, 4305–4314 (1986).
Treisman, R. Cancer Biol. 1, 47–58 (1990).
Herrera, R. E., Shaw, P. E. & Nordheim, A. Nature 340, 68–70 (1989).
König, H. Nucleic Acids Res. 19, 3607–3611 (1991).
Shaw, P. E., Schröter, H. & Nordheim, A. Cell 56, 563–572 (1989).
Graham, R. & Gilman, M. Science 251, 189–192 (1991).
Gutman, A., Wasylyk, C. & Wasylyk, B. Molec. cell. Biol. 11, 5381–5387 (1991).
Treisman, R. Cell 46, 567–574 (1986).
Karim, F. D. et al. Genes Dev. 4, 1451–1453 (1990).
Rao, V. N. & Reddy, E. S. P. Oncogene (in the press).
Reddy, E. S. P. & Rao, V. N. Oncogene (in the press).
Rao, V. N. et al. Science 244, 66–70 (1989).
Mueller, C. G. F. & Nordheim, A. EMBO J. (in the press).
Gutman, A. & Wasylyk, B. Trends Genet. 7, 49–54 (1991).
Norman, C., Runswick, M., Pollock, R. M. & Treisman, R. Cell 55, 989–1003 (1988).
Schröter, H., Mueller, C. G. F., Meese, K. & Nordheim, A. EMBO J. 9, 1123–1130 (1990).
Watson, D. K. et al. Proc. natn. Acad. Sci. U.S.A. 85, 7862–7866 (1988).
Reddy, E. S. P. & Rao, V. N. Cancer Res. 50, 5013–5016 (1990).
Dolan, J. W. & Fields, S., Biochim. biophys. Acta. 1088, 155–169 (1991).
Wasylyk, B. et al. Nature 346, 191–193 (1990).
Bosselut, R. et al. EMBO J. 9, 3137–3144 (1990).
Gunther, C. V., Nye, J. A., Bryer, R. S. & Graves, B. J. Genes Dev. 4, 667–679 (1990).
Thompson, C. C., Brown, T. A. & McKnight, S. L. Science 253, 762–768 (1991).
Turc-Carel, C. et al. Proc. natn. Acad. Sci. U.S.A. 84, 1981–1985 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hipskind, R., Roa, V., Muller, C. et al. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature 354, 531–534 (1991). https://doi.org/10.1038/354531a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/354531a0
This article is cited by
-
GPX4 suppresses ferroptosis to promote malignant progression of endometrial carcinoma via transcriptional activation by ELK1
BMC Cancer (2022)
-
EGFR activates GDH1 transcription to promote glutamine metabolism through MEK/ERK/ELK1 pathway in glioblastoma
Oncogene (2020)
-
miR-597-5p inhibits cell growth and promotes cell apoptosis by targeting ELK1 in pancreatic cancer
Human Cell (2020)
-
Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes
Genes & Genomics (2018)
-
Pancancer modelling predicts the context-specific impact of somatic mutations on transcriptional programs
Nature Communications (2017)
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.
