Abstract
Transcriptional activation of the c-fos gene in mouse S49 cells by the adenovirus 243-amino-acid E1A protein depends on domains of E1A that are also required for transformation and that bind the cellular protein p300. Activation additionally depends on stimulation of endogenous cyclic AMP (cAMP)-dependent protein kinase by analogs or inducers of cAMP. Transient transfection assays were used to analyze the c-fos promoter for sequences that confer responsiveness to E1A. Linker substitution and point mutants revealed that transcriptional activation by E1A depended on a cAMP response element (CRE) located at -67 relative to the start site of transcription and a neighboring binding site for transcription factor YY1 located at -54. A 22-bp sequence containing the -67 CRE and the -54 YY1 site was sufficient to confer responsiveness to a minimal E1B promoter and was termed the c-fos E1A response element (ERE). Function of the c-fos ERE depended on both the CRE and the YY1 site, since mutation of either site resulted in a loss of responsiveness to E1A. These results imply a specific functional interaction between CRE-binding proteins, transcription factor YY1, and E1A in the regulation of the c-fos gene.
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- Arany Z., Sellers W. R., Livingston D. M., Eckner R. E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. Cell. 1994 Jun 17;77(6):799–800. doi: 10.1016/0092-8674(94)90127-9. [DOI] [PubMed] [Google Scholar]
- Bagchi S., Weinmann R., Raychaudhuri P. The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F. Cell. 1991 Jun 14;65(6):1063–1072. doi: 10.1016/0092-8674(91)90558-g. [DOI] [PubMed] [Google Scholar]
- Bandara L. R., Adamczewski J. P., Hunt T., La Thangue N. B. Cyclin A and the retinoblastoma gene product complex with a common transcription factor. Nature. 1991 Jul 18;352(6332):249–251. doi: 10.1038/352249a0. [DOI] [PubMed] [Google Scholar]
- Bandara L. R., La Thangue N. B. Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. Nature. 1991 Jun 6;351(6326):494–497. doi: 10.1038/351494a0. [DOI] [PubMed] [Google Scholar]
- Boyer T. G., Berk A. J. Functional interaction of adenovirus E1A with holo-TFIID. Genes Dev. 1993 Sep;7(9):1810–1823. doi: 10.1101/gad.7.9.1810. [DOI] [PubMed] [Google Scholar]
- Cao L., Faha B., Dembski M., Tsai L. H., Harlow E., Dyson N. Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F. Nature. 1992 Jan 9;355(6356):176–179. doi: 10.1038/355176a0. [DOI] [PubMed] [Google Scholar]
- Chatton B., Bocco J. L., Gaire M., Hauss C., Reimund B., Goetz J., Kedinger C. Transcriptional activation by the adenovirus larger E1a product is mediated by members of the cellular transcription factor ATF family which can directly associate with E1a. Mol Cell Biol. 1993 Jan;13(1):561–570. doi: 10.1128/mcb.13.1.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chellappan S. P., Hiebert S., Mudryj M., Horowitz J. M., Nevins J. R. The E2F transcription factor is a cellular target for the RB protein. Cell. 1991 Jun 14;65(6):1053–1061. doi: 10.1016/0092-8674(91)90557-f. [DOI] [PubMed] [Google Scholar]
- Chittenden T., Livingston D. M., Kaelin W. G., Jr The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein. Cell. 1991 Jun 14;65(6):1073–1082. doi: 10.1016/0092-8674(91)90559-h. [DOI] [PubMed] [Google Scholar]
- Cobrinik D., Whyte P., Peeper D. S., Jacks T., Weinberg R. A. Cell cycle-specific association of E2F with the p130 E1A-binding protein. Genes Dev. 1993 Dec;7(12A):2392–2404. doi: 10.1101/gad.7.12a.2392. [DOI] [PubMed] [Google Scholar]
- Devoto S. H., Mudryj M., Pines J., Hunter T., Nevins J. R. A cyclin A-protein kinase complex possesses sequence-specific DNA binding activity: p33cdk2 is a component of the E2F-cyclin A complex. Cell. 1992 Jan 10;68(1):167–176. doi: 10.1016/0092-8674(92)90215-x. [DOI] [PubMed] [Google Scholar]
- Dyson N., Harlow E. Adenovirus E1A targets key regulators of cell proliferation. Cancer Surv. 1992;12:161–195. [PubMed] [Google Scholar]
- Eckner R., Ewen M. E., Newsome D., Gerdes M., DeCaprio J. A., Lawrence J. B., Livingston D. M. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 1994 Apr 15;8(8):869–884. doi: 10.1101/gad.8.8.869. [DOI] [PubMed] [Google Scholar]
- Engel D. A., Muller U., Gedrich R. W., Eubanks J. S., Shenk T. Induction of c-fos mRNA and AP-1 DNA-binding activity by cAMP in cooperation with either the adenovirus 243- or the adenovirus 289-amino acid E1A protein. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3957–3961. doi: 10.1073/pnas.88.9.3957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flint J., Shenk T. Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet. 1989;23:141–161. doi: 10.1146/annurev.ge.23.120189.001041. [DOI] [PubMed] [Google Scholar]
- Gedrich R. W., Bayley S. T., Engel D. A. Induction of AP-1 DNA-binding activity and c-fos mRNA by the adenovirus 243R E1A protein and cyclic AMP requires domains necessary for transformation. J Virol. 1992 Oct;66(10):5849–5859. doi: 10.1128/jvi.66.10.5849-5859.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geisberg J. V., Lee W. S., Berk A. J., Ricciardi R. P. The zinc finger region of the adenovirus E1A transactivating domain complexes with the TATA box binding protein. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2488–2492. doi: 10.1073/pnas.91.7.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haley K. P., Overhauser J., Babiss L. E., Ginsberg H. S., Jones N. C. Transformation properties of type 5 adenovirus mutants that differentially express the E1A gene products. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5734–5738. doi: 10.1073/pnas.81.18.5734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardy S., Shenk T. Adenoviral control regions activated by E1A and the cAMP response element bind to the same factor. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4171–4175. doi: 10.1073/pnas.85.12.4171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hearing P., Shenk T. Sequence-independent autoregulation of the adenovirus type 5 E1A transcription unit. Mol Cell Biol. 1985 Nov;5(11):3214–3221. doi: 10.1128/mcb.5.11.3214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hipskind R. A., Nordheim A. Functional dissection in vitro of the human c-fos promoter. J Biol Chem. 1991 Oct 15;266(29):19583–19592. [PubMed] [Google Scholar]
- Howe J. A., Mymryk J. S., Egan C., Branton P. E., Bayley S. T. Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5883–5887. doi: 10.1073/pnas.87.15.5883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter T., Pines J. Cyclins and cancer. Cell. 1991 Sep 20;66(6):1071–1074. doi: 10.1016/0092-8674(91)90028-w. [DOI] [PubMed] [Google Scholar]
- Ishii T., Shimizu M., Kanayama Y., Nakada S., Nojima H., Oda K. Differential activation of cyclin and cyclin-dependent kinase genes by adenovirus E1A12S cDNA product. Exp Cell Res. 1993 Oct;208(2):407–414. doi: 10.1006/excr.1993.1262. [DOI] [PubMed] [Google Scholar]
- Jelsma T. N., Howe J. A., Mymryk J. S., Evelegh C. M., Cunniff N. F., Bayley S. T. Sequences in E1A proteins of human adenovirus 5 required for cell transformation, repression of a transcriptional enhancer, and induction of proliferating cell nuclear antigen. Virology. 1989 Jul;171(1):120–130. doi: 10.1016/0042-6822(89)90518-7. [DOI] [PubMed] [Google Scholar]
- Kaddurah-Daouk R., Lillie J. W., Daouk G. H., Green M. R., Kingston R., Schimmel P. Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a. Mol Cell Biol. 1990 Apr;10(4):1476–1483. doi: 10.1128/mcb.10.4.1476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kraus V. B., Moran E., Nevins J. R. Promoter-specific trans-activation by the adenovirus E1A12S product involves separate E1A domains. Mol Cell Biol. 1992 Oct;12(10):4391–4399. doi: 10.1128/mcb.12.10.4391. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee W. S., Kao C. C., Bryant G. O., Liu X., Berk A. J. Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell. 1991 Oct 18;67(2):365–376. doi: 10.1016/0092-8674(91)90188-5. [DOI] [PubMed] [Google Scholar]
- Lewis B. A., Tullis G., Seto E., Horikoshi N., Weinmann R., Shenk T. Adenovirus E1A proteins interact with the cellular YY1 transcription factor. J Virol. 1995 Mar;69(3):1628–1636. doi: 10.1128/jvi.69.3.1628-1636.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
- Liu F., Green M. R. Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains. Nature. 1994 Apr 7;368(6471):520–525. doi: 10.1038/368520a0. [DOI] [PubMed] [Google Scholar]
- Miller C. P., Lin J. C., Habener J. F. Transcription of the rat glucagon gene by the cyclic AMP response element-binding protein CREB is modulated by adjacent CREB-associated proteins. Mol Cell Biol. 1993 Nov;13(11):7080–7090. doi: 10.1128/mcb.13.11.7080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montell C., Courtois G., Eng C., Berk A. Complete transformation by adenovirus 2 requires both E1A proteins. Cell. 1984 Apr;36(4):951–961. doi: 10.1016/0092-8674(84)90045-x. [DOI] [PubMed] [Google Scholar]
- Moran E. Interaction of adenoviral proteins with pRB and p53. FASEB J. 1993 Jul;7(10):880–885. doi: 10.1096/fasebj.7.10.8344487. [DOI] [PubMed] [Google Scholar]
- Morris G. F., Labrie C., Mathews M. B. Modulation of transcriptional activation of the proliferating cell nuclear antigen promoter by the adenovirus E1A 243-residue oncoprotein depends on proximal activators. Mol Cell Biol. 1994 Jan;14(1):543–553. doi: 10.1128/mcb.14.1.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mudryj M., Devoto S. H., Hiebert S. W., Hunter T., Pines J., Nevins J. R. Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell. 1991 Jun 28;65(7):1243–1253. doi: 10.1016/0092-8674(91)90019-u. [DOI] [PubMed] [Google Scholar]
- Müller U., Roberts M. P., Engel D. A., Doerfler W., Shenk T. Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. Genes Dev. 1989 Dec;3(12A):1991–2002. doi: 10.1101/gad.3.12a.1991. [DOI] [PubMed] [Google Scholar]
- Natesan S., Gilman M. Z. DNA bending and orientation-dependent function of YY1 in the c-fos promoter. Genes Dev. 1993 Dec;7(12B):2497–2509. doi: 10.1101/gad.7.12b.2497. [DOI] [PubMed] [Google Scholar]
- Nevins J. R. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science. 1992 Oct 16;258(5081):424–429. doi: 10.1126/science.1411535. [DOI] [PubMed] [Google Scholar]
- Sassone-Corsi P., Borrelli E. Promoter trans-activation of protooncogenes c-fos and c-myc, but not c-Ha-ras, by products of adenovirus early region 1A. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6430–6433. doi: 10.1073/pnas.84.18.6430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shi Y., Seto E., Chang L. S., Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18;67(2):377–388. doi: 10.1016/0092-8674(91)90189-6. [DOI] [PubMed] [Google Scholar]
- Shirodkar S., Ewen M., DeCaprio J. A., Morgan J., Livingston D. M., Chittenden T. The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell. 1992 Jan 10;68(1):157–166. doi: 10.1016/0092-8674(92)90214-w. [DOI] [PubMed] [Google Scholar]
- Simon M. C., Kitchener K., Kao H. T., Hickey E., Weber L., Voellmy R., Heintz N., Nevins J. R. Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product. Mol Cell Biol. 1987 Aug;7(8):2884–2890. doi: 10.1128/mcb.7.8.2884. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slansky J. E., Li Y., Kaelin W. G., Farnham P. J. A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter. Mol Cell Biol. 1993 Mar;13(3):1610–1618. doi: 10.1128/mcb.13.3.1610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg R. A. The retinoblastoma gene and cell growth control. Trends Biochem Sci. 1990 May;15(5):199–202. doi: 10.1016/0968-0004(90)90162-5. [DOI] [PubMed] [Google Scholar]
- Whyte P., Williamson N. M., Harlow E. Cellular targets for transformation by the adenovirus E1A proteins. Cell. 1989 Jan 13;56(1):67–75. doi: 10.1016/0092-8674(89)90984-7. [DOI] [PubMed] [Google Scholar]
- Winberg G., Shenk T. Dissection of overlapping functions within the adenovirus type 5 E1A gene. EMBO J. 1984 Aug;3(8):1907–1912. doi: 10.1002/j.1460-2075.1984.tb02066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zerler B., Moran B., Maruyama K., Moomaw J., Grodzicker T., Ruley H. E. Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells. Mol Cell Biol. 1986 Mar;6(3):887–899. doi: 10.1128/mcb.6.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Dam H., Duyndam M., Rottier R., Bosch A., de Vries-Smits L., Herrlich P., Zantema A., Angel P., van der Eb A. J. Heterodimer formation of cJun and ATF-2 is responsible for induction of c-jun by the 243 amino acid adenovirus E1A protein. EMBO J. 1993 Feb;12(2):479–487. doi: 10.1002/j.1460-2075.1993.tb05680.x. [DOI] [PMC free article] [PubMed] [Google Scholar]