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. 1989 May;8(5):1455–1460. doi: 10.1002/j.1460-2075.1989.tb03528.x

Transcription factors AP-3 and AP-2 interact with the SV40 enhancer in a mutually exclusive manner.

F Mercurio 1, M Karin 1
PMCID: PMC400974  PMID: 2548845

Abstract

The 'core' sequence is critical for efficient transcriptional activity of the SV40 enhancer. Moreover, the core was shown to be involved in a signal transduction pathway elicited by treatment of cells with phorbol ester tumor promoters. We report here the identification and characterization of activator protein-3 (AP-3), which recognizes the core element. AP-3 was purified to near homogeneity and identified as a 48K polypeptide. The purified protein is an efficient transcriptional activator in vitro. In addition, we show that AP-3 and a second factor that recognizes the SV40 enhancer, AP-2, interact in a mutually exclusive manner. These studies should facilitate understanding of the mechanism by which the SV40 enhancer achieves its characteristic broad cell-type specificity.

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Selected References

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  1. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  2. Bodner M., Karin M. A pituitary-specific trans-acting factor can stimulate transcription from the growth hormone promoter in extracts of nonexpressing cells. Cell. 1987 Jul 17;50(2):267–275. doi: 10.1016/0092-8674(87)90222-4. [DOI] [PubMed] [Google Scholar]
  3. Briggs M. R., Kadonaga J. T., Bell S. P., Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. doi: 10.1126/science.3529394. [DOI] [PubMed] [Google Scholar]
  4. Cato A. C., Skroch P., Weinmann J., Butkeraitis P., Ponta H. DNA sequences outside the receptor-binding sites differently modulate the responsiveness of the mouse mammary tumour virus promoter to various steroid hormones. EMBO J. 1988 May;7(5):1403–1410. doi: 10.1002/j.1460-2075.1988.tb02957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  6. Chiu R., Imagawa M., Imbra R. J., Bockoven J. R., Karin M. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature. 1987 Oct 15;329(6140):648–651. doi: 10.1038/329648a0. [DOI] [PubMed] [Google Scholar]
  7. Clark L., Pollock R. M., Hay R. T. Identification and purification of EBP1: a HeLa cell protein that binds to a region overlapping the 'core' of the SV40 enhancer. Genes Dev. 1988 Aug;2(8):991–1002. doi: 10.1101/gad.2.8.991. [DOI] [PubMed] [Google Scholar]
  8. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  9. Gorman C. M., Lane D. P., Watson C. J., Rigby P. W. The regulation of gene expression in murine teratocarcinoma cells. Cold Spring Harb Symp Quant Biol. 1985;50:701–706. doi: 10.1101/sqb.1985.050.01.086. [DOI] [PubMed] [Google Scholar]
  10. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  11. Hager D. A., Burgess R. R. Elution of proteins from sodium dodecyl sulfate-polyacrylamide gels, removal of sodium dodecyl sulfate, and renaturation of enzymatic activity: results with sigma subunit of Escherichia coli RNA polymerase, wheat germ DNA topoisomerase, and other enzymes. Anal Biochem. 1980 Nov 15;109(1):76–86. doi: 10.1016/0003-2697(80)90013-5. [DOI] [PubMed] [Google Scholar]
  12. Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [PubMed] [Google Scholar]
  13. Herr W., Gluzman Y. Duplications of a mutated simian virus 40 enhancer restore its activity. Nature. 1985 Feb 21;313(6004):711–714. doi: 10.1038/313711a0. [DOI] [PubMed] [Google Scholar]
  14. Imagawa M., Chiu R., Karin M. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. 1987 Oct 23;51(2):251–260. doi: 10.1016/0092-8674(87)90152-8. [DOI] [PubMed] [Google Scholar]
  15. Kadonaga J. T., Tjian R. Affinity purification of sequence-specific DNA binding proteins. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5889–5893. doi: 10.1073/pnas.83.16.5889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kawakami K., Scheidereit C., Roeder R. G. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700–4704. doi: 10.1073/pnas.85.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  18. Mermod N., Williams T. J., Tjian R. Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 1988 Apr 7;332(6164):557–561. doi: 10.1038/332557a0. [DOI] [PubMed] [Google Scholar]
  19. Mitchell P. J., Wang C., Tjian R. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Cell. 1987 Sep 11;50(6):847–861. doi: 10.1016/0092-8674(87)90512-5. [DOI] [PubMed] [Google Scholar]
  20. Nomiyama H., Fromental C., Xiao J. H., Chambon P. Cell-specific activity of the constituent elements of the simian virus 40 enhancer. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7881–7885. doi: 10.1073/pnas.84.22.7881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ondek B., Shepard A., Herr W. Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities. EMBO J. 1987 Apr;6(4):1017–1025. doi: 10.1002/j.1460-2075.1987.tb04854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pfeifer K., Prezant T., Guarente L. Yeast HAP1 activator binds to two upstream activation sites of different sequence. Cell. 1987 Apr 10;49(1):19–27. doi: 10.1016/0092-8674(87)90751-3. [DOI] [PubMed] [Google Scholar]
  23. Sassone-Corsi P., Fromental C., Chambon P. A trans-acting factor represses the activity of the polyoma virus enhancer in undifferentiated embryonal carcinoma cells. Oncogene Res. 1987 Jul;1(2):113–119. [PubMed] [Google Scholar]
  24. Schirm S., Jiricny J., Schaffner W. The SV40 enhancer can be dissected into multiple segments, each with a different cell type specificity. Genes Dev. 1987 Mar;1(1):65–74. doi: 10.1101/gad.1.1.65. [DOI] [PubMed] [Google Scholar]
  25. Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26;47(6):921–928. doi: 10.1016/0092-8674(86)90807-x. [DOI] [PubMed] [Google Scholar]
  26. Serfling E., Barthelmäs R., Pfeuffer I., Schenk B., Zarius S., Swoboda R., Mercurio F., Karin M. Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes. EMBO J. 1989 Feb;8(2):465–473. doi: 10.1002/j.1460-2075.1989.tb03399.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sleigh M. J., Lockett T. J. SV40 enhancer activation during retinoic acid-induced differentiation of F9 embryonal carcinoma cells. EMBO J. 1985 Dec 30;4(13B):3831–3837. doi: 10.1002/j.1460-2075.1985.tb04155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weiher H., König M., Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. doi: 10.1126/science.6297005. [DOI] [PubMed] [Google Scholar]
  29. Xiao J. H., Davidson I., Macchi M., Rosales R., Vigneron M., Staub A., Chambon P. In vitro binding of several cell-specific and ubiquitous nuclear proteins to the GT-I motif of the SV40 enhancer. Genes Dev. 1987 Oct;1(8):794–807. doi: 10.1101/gad.1.8.794. [DOI] [PubMed] [Google Scholar]
  30. Yee J. K., Moores J. C., Jolly D. J., Wolff J. A., Respess J. G., Friedmann T. Gene expression from transcriptionally disabled retroviral vectors. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5197–5201. doi: 10.1073/pnas.84.15.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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