Abstract
We have identified oncogene-responsive sequences in the human c-fos promoter that mediate induction of transcription by several nonnuclear oncoproteins and the tumor promoter TPA. These sequences are regulated in a cell-specific manner. (i) In NIH 3T3 cells, the CArG box of the c-fos promoter is sufficient to mediate activation by oncogenes. (ii) In contrast, in HeLa cells, additional flanking sequences are also required, including the outer arm of the serum response element and the FAP site. We also show that the serum response factor, which binds to the CArG box, activates transcription in vivo in NIH 3T3 cells but not in HeLa cells. Finally, we present evidence that the intracellular level of the c-Fos protein could be a major determinant of cell-specific regulation of these oncogene-responsive elements of the c-fos promoter.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
- Chavrier P., Janssen-Timmen U., Mattéi M. G., Zerial M., Bravo R., Charnay P. Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos. Mol Cell Biol. 1989 Feb;9(2):787–797. doi: 10.1128/mcb.9.2.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christy B. A., Lau L. F., Nathans D. A gene activated in mouse 3T3 cells by serum growth factors encodes a protein with "zinc finger" sequences. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7857–7861. doi: 10.1073/pnas.85.21.7857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisch T. M., Prywes R., Roeder R. G. An AP1-binding site in the c-fos gene can mediate induction by epidermal growth factor and 12-O-tetradecanoyl phorbol-13-acetate. Mol Cell Biol. 1989 Mar;9(3):1327–1331. doi: 10.1128/mcb.9.3.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilman M. Z. The c-fos serum response element responds to protein kinase C-dependent and -independent signals but not to cyclic AMP. Genes Dev. 1988 Apr;2(4):394–402. doi: 10.1101/gad.2.4.394. [DOI] [PubMed] [Google Scholar]
- Gius D., Cao X. M., Rauscher F. J., 3rd, Cohen D. R., Curran T., Sukhatme V. P. Transcriptional activation and repression by Fos are independent functions: the C terminus represses immediate-early gene expression via CArG elements. Mol Cell Biol. 1990 Aug;10(8):4243–4255. doi: 10.1128/mcb.10.8.4243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham R., Gilman M. Distinct protein targets for signals acting at the c-fos serum response element. Science. 1991 Jan 11;251(4990):189–192. doi: 10.1126/science.1898992. [DOI] [PubMed] [Google Scholar]
- Green S., Issemann I., Sheer E. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988 Jan 11;16(1):369–369. doi: 10.1093/nar/16.1.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg M. E., Siegfried Z., Ziff E. B. Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro. Mol Cell Biol. 1987 Mar;7(3):1217–1225. doi: 10.1128/mcb.7.3.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gutman A., Wasylyk B. Nuclear targets for transcription regulation by oncogenes. Trends Genet. 1991 Feb;7(2):49–54. doi: 10.1016/0168-9525(91)90231-E. [DOI] [PubMed] [Google Scholar]
- Gutman A., Wasylyk B. The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J. 1990 Jul;9(7):2241–2246. doi: 10.1002/j.1460-2075.1990.tb07394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayes T. E., Sengupta P., Cochran B. H. The human c-fos serum response factor and the yeast factors GRM/PRTF have related DNA-binding specificities. Genes Dev. 1988 Dec;2(12B):1713–1722. doi: 10.1101/gad.2.12b.1713. [DOI] [PubMed] [Google Scholar]
- Herrera R. E., Shaw P. E., Nordheim A. Occupation of the c-fos serum response element in vivo by a multi-protein complex is unaltered by growth factor induction. Nature. 1989 Jul 6;340(6228):68–70. doi: 10.1038/340068a0. [DOI] [PubMed] [Google Scholar]
- Jamal S., Ziff E. Transactivation of c-fos and beta-actin genes by raf as a step in early response to transmembrane signals. Nature. 1990 Mar 29;344(6265):463–466. doi: 10.1038/344463a0. [DOI] [PubMed] [Google Scholar]
- Jarvis E. E., Clark K. L., Sprague G. F., Jr The yeast transcription activator PRTF, a homolog of the mammalian serum response factor, is encoded by the MCM1 gene. Genes Dev. 1989 Jul;3(7):936–945. doi: 10.1101/gad.3.7.936. [DOI] [PubMed] [Google Scholar]
- König H., Ponta H., Rahmsdorf U., Büscher M., Schönthal A., Rahmsdorf H. J., Herrlich P. Autoregulation of fos: the dyad symmetry element as the major target of repression. EMBO J. 1989 Sep;8(9):2559–2566. doi: 10.1002/j.1460-2075.1989.tb08394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leung S., Miyamoto N. G. Point mutational analysis of the human c-fos serum response factor binding site. Nucleic Acids Res. 1989 Feb 11;17(3):1177–1195. doi: 10.1093/nar/17.3.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lucibello F. C., Lowag C., Neuberg M., Müller R. trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation. Cell. 1989 Dec 22;59(6):999–1007. doi: 10.1016/0092-8674(89)90756-3. [DOI] [PubMed] [Google Scholar]
- Manak J. R., de Bisschop N., Kris R. M., Prywes R. Casein kinase II enhances the DNA binding activity of serum response factor. Genes Dev. 1990 Jun;4(6):955–967. doi: 10.1101/gad.4.6.955. [DOI] [PubMed] [Google Scholar]
- Norman C., Runswick M., Pollock R., Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988 Dec 23;55(6):989–1003. doi: 10.1016/0092-8674(88)90244-9. [DOI] [PubMed] [Google Scholar]
- Passmore S., Elble R., Tye B. K. A protein involved in minichromosome maintenance in yeast binds a transcriptional enhancer conserved in eukaryotes. Genes Dev. 1989 Jul;3(7):921–935. doi: 10.1101/gad.3.7.921. [DOI] [PubMed] [Google Scholar]
- Prywes R., Roeder R. G. Purification of the c-fos enhancer-binding protein. Mol Cell Biol. 1987 Oct;7(10):3482–3489. doi: 10.1128/mcb.7.10.3482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rivera V. M., Greenberg M. E. Growth factor-induced gene expression: the ups and downs of c-fos regulation. New Biol. 1990 Sep;2(9):751–758. [PubMed] [Google Scholar]
- Rivera V. M., Sheng M., Greenberg M. E. The inner core of the serum response element mediates both the rapid induction and subsequent repression of c-fos transcription following serum stimulation. Genes Dev. 1990 Feb;4(2):255–268. doi: 10.1101/gad.4.2.255. [DOI] [PubMed] [Google Scholar]
- Ryan W. A., Jr, Franza B. R., Jr, Gilman M. Z. Two distinct cellular phosphoproteins bind to the c-fos serum response element. EMBO J. 1989 Jun;8(6):1785–1792. doi: 10.1002/j.1460-2075.1989.tb03572.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schönthal A., Feramisco J. R. Different promoter elements are required for the induced expression of c-fos and c-jun proto-oncogenes by the v-mos oncogene product. New Biol. 1990 Feb;2(2):143–150. [PubMed] [Google Scholar]
- Shaw P. E., Frasch S., Nordheim A. Repression of c-fos transcription is mediated through p67SRF bound to the SRE. EMBO J. 1989 Sep;8(9):2567–2574. doi: 10.1002/j.1460-2075.1989.tb08395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw P. E., Schröter H., Nordheim A. The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Cell. 1989 Feb 24;56(4):563–572. doi: 10.1016/0092-8674(89)90579-5. [DOI] [PubMed] [Google Scholar]
- Stacey D. W., Watson T., Kung H. F., Curran T. Microinjection of transforming ras protein induces c-fos expression. Mol Cell Biol. 1987 Jan;7(1):523–527. doi: 10.1128/mcb.7.1.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stumpo D. J., Stewart T. N., Gilman M. Z., Blackshear P. J. Identification of c-fos sequences involved in induction by insulin and phorbol esters. J Biol Chem. 1988 Feb 5;263(4):1611–1614. [PubMed] [Google Scholar]
- Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell. 1986 Aug 15;46(4):567–574. doi: 10.1016/0092-8674(86)90882-2. [DOI] [PubMed] [Google Scholar]
- Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
- Velcich A., Ziff E. B. Functional analysis of an isolated fos promoter element with AP-1 site homology reveals cell type-specific transcriptional properties. Mol Cell Biol. 1990 Dec;10(12):6273–6282. doi: 10.1128/mcb.10.12.6273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walsh K. Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes. Mol Cell Biol. 1989 May;9(5):2191–2201. doi: 10.1128/mcb.9.5.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wasylyk C., Flores P., Gutman A., Wasylyk B. PEA3 is a nuclear target for transcription activation by non-nuclear oncogenes. EMBO J. 1989 Nov;8(11):3371–3378. doi: 10.1002/j.1460-2075.1989.tb08500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wasylyk C., Imler J. L., Wasylyk B. Transforming but not immortalizing oncogenes activate the transcription factor PEA1. EMBO J. 1988 Aug;7(8):2475–2483. doi: 10.1002/j.1460-2075.1988.tb03094.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu S. F., von Rüden T., Kantoff P. W., Garber C., Seiberg M., Rüther U., Anderson W. F., Wagner E. F., Gilboa E. Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc Natl Acad Sci U S A. 1986 May;83(10):3194–3198. doi: 10.1073/pnas.83.10.3194. [DOI] [PMC free article] [PubMed] [Google Scholar]