Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1995 Sep 25;23(18):3732–3741. doi: 10.1093/nar/23.18.3732

Transcription factors RFX1/EF-C and ATF-1 associate with the adenovirus E1A-responsive element of the human proliferating cell nuclear antigen promoter.

C Labrie 1, B H Lee 1, M B Mathews 1
PMCID: PMC307273  PMID: 7479004

Abstract

The proliferating cell nuclear antigen (PCNA) is an adenovirus E1A-inducible factor that is intimately linked to the processes of DNA replication and cell cycle regulation. Previously, we defined a novel cis-acting element, the PCNA E1A-responsive element (PERE), that confers induction by the E1A 243R oncoprotein upon the human PCNA promoter. To better understand the regulation of PCNA expression by E1A 243R, we have identified cellular transcription factors that associate with the PERE. In electrophoretic mobility shift assays, the PERE formed three major complexes (P1, P2 and P3) with proteins in nuclear extracts from HeLa or 293 cells. Formation of complexes P2 and P3, which correlates with PCNA promoter activity in vivo, requires the activating transcription factor (ATF) binding site found within the PERE [Labrie et al. (1993) Mol. Cell. Biol., 13, 1697-1707]. Antibody interference experiments and mobility shift assays performed with in vitro-synthesized protein indicated that the transcription factor ATF-1 is a major component of these complexes. Similar assays demonstrated that the hepatitis B virus enhancer-associated protein RFX1 constitutes a major component of the P1 complex. In addition, we examined the binding of proteins to the minimal E1A-responsive promoter to identify other factors important for transcription from the PCNA promoter. Mobility shift assays revealed that a fragment encompassing the region from -87 to +62 relative to the transcription initiation site forms at least five complexes, EH1-EH5, with HeLa cell nuclear extracts. The transcription factor YY1 associates with the initiator element of the PCNA promoter. The identification of these transcription factors will allow their roles in the activation of PCNA by E1A to be evaluated.

Full text

PDF
3736

Images in this article

3734Image
on p.3734
3735Image
on p.3735
3736Image
on p.3736
3736Image
on p.3736
3737Image
on p.3737
3738Image
on p.3738
3739Image
on p.3739

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben-Levy R., Faktor O., Berger I., Shaul Y. Cellular factors that interact with the hepatitis B virus enhancer. Mol Cell Biol. 1989 Apr;9(4):1804–1809. doi: 10.1128/mcb.9.4.1804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brand S. R., Bernstein R. M., Mathews M. B. Trimeric structure of human proliferating cell nuclear antigen. Implications for enzymatic function and autoantibody recognition. J Immunol. 1994 Oct 1;153(7):3070–3078. [PubMed] [Google Scholar]
  3. Bravo R., Frank R., Blundell P. A., Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987 Apr 2;326(6112):515–517. doi: 10.1038/326515a0. [DOI] [PubMed] [Google Scholar]
  4. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dikstein R., Heffetz D., Ben-Neriah Y., Shaul Y. c-abl has a sequence-specific enhancer binding activity. Cell. 1992 May 29;69(5):751–757. doi: 10.1016/0092-8674(92)90287-m. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Flint K. J., Jones N. C. Differential regulation of three members of the ATF/CREB family of DNA-binding proteins. Oncogene. 1991 Nov;6(11):2019–2026. [PubMed] [Google Scholar]
  8. Hai T. W., Liu F., Coukos W. J., Green M. R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. doi: 10.1101/gad.3.12b.2083. [DOI] [PubMed] [Google Scholar]
  9. Huang D., Shipman-Appasamy P. M., Orten D. J., Hinrichs S. H., Prystowsky M. B. Promoter activity of the proliferating-cell nuclear antigen gene is associated with inducible CRE-binding proteins in interleukin 2-stimulated T lymphocytes. Mol Cell Biol. 1994 Jun;14(6):4233–4243. doi: 10.1128/mcb.14.6.4233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hurst H. C., Masson N., Jones N. C., Lee K. A. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43. Mol Cell Biol. 1990 Dec;10(12):6192–6203. doi: 10.1128/mcb.10.12.6192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hurst H. C., Totty N. F., Jones N. C. Identification and functional characterisation of the cellular activating transcription factor 43 (ATF-43) protein. Nucleic Acids Res. 1991 Sep 11;19(17):4601–4609. doi: 10.1093/nar/19.17.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jaskulski D., deRiel J. K., Mercer W. E., Calabretta B., Baserga R. Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. Science. 1988 Jun 10;240(4858):1544–1546. doi: 10.1126/science.2897717. [DOI] [PubMed] [Google Scholar]
  13. Kannabiran C., Morris G. F., Labrie C., Mathews M. B. The adenovirus E1A 12S product displays functional redundancy in activating the human proliferating cell nuclear antigen promoter. J Virol. 1993 Jan;67(1):507–515. doi: 10.1128/jvi.67.1.507-515.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Labrie C., Morris G. F., Mathews M. B. A complex promoter element mediates transactivation of the human proliferating cell nuclear antigen promoter by the 243-residue adenovirus E1A oncoprotein. Mol Cell Biol. 1993 Mar;13(3):1697–1707. doi: 10.1128/mcb.13.3.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Liu F., Green M. R. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990 Jun 29;61(7):1217–1224. doi: 10.1016/0092-8674(90)90686-9. [DOI] [PubMed] [Google Scholar]
  16. Liu F., Thompson M. A., Wagner S., Greenberg M. E., Green M. R. Activating transcription factor-1 can mediate Ca(2+)- and cAMP-inducible transcriptional activation. J Biol Chem. 1993 Mar 25;268(9):6714–6720. [PubMed] [Google Scholar]
  17. Liu Y. C., Marraccino R. L., Keng P. C., Bambara R. A., Lord E. M., Chou W. G., Zain S. B. Requirement for proliferating cell nuclear antigen expression during stages of the Chinese hamster ovary cell cycle. Biochemistry. 1989 Apr 4;28(7):2967–2974. doi: 10.1021/bi00433a034. [DOI] [PubMed] [Google Scholar]
  18. Maekawa T., Matsuda S., Fujisawa J., Yoshida M., Ishii S. Cyclic AMP response element-binding protein, CRE-BP1, mediates the E1A-induced but not the Tax-induced trans-activation. Oncogene. 1991 Apr;6(4):627–632. [PubMed] [Google Scholar]
  19. Mathews M. B., Bernstein R. M., Franza B. R., Jr, Garrels J. I. Identity of the proliferating cell nuclear antigen and cyclin. Nature. 1984 May 24;309(5966):374–376. doi: 10.1038/309374a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Morris G. F., Mathews M. B. The adenovirus E1A transforming protein activates the proliferating cell nuclear antigen promoter via an activating transcription factor site. J Virol. 1991 Dec;65(12):6397–6406. doi: 10.1128/jvi.65.12.6397-6406.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Ostapchuk P., Scheirle G., Hearing P. Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region. Mol Cell Biol. 1989 Jul;9(7):2787–2797. doi: 10.1128/mcb.9.7.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pietrzkowski Z., Alder H., Chang C. D., Ku D. H., Baserga R. Characterization of an enhancer-like structure in the promoter region of the proliferating cell nuclear antigen (PCNA) gene. Exp Cell Res. 1991 Apr;193(2):283–290. doi: 10.1016/0014-4827(91)90098-f. [DOI] [PubMed] [Google Scholar]
  25. Prelich G., Kostura M., Marshak D. R., Mathews M. B., Stillman B. The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature. 1987 Apr 2;326(6112):471–475. doi: 10.1038/326471a0. [DOI] [PubMed] [Google Scholar]
  26. Prelich G., Tan C. K., Kostura M., Mathews M. B., So A. G., Downey K. M., Stillman B. Functional identity of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature. 1987 Apr 2;326(6112):517–520. doi: 10.1038/326517a0. [DOI] [PubMed] [Google Scholar]
  27. Reith W., Herrero-Sanchez C., Kobr M., Silacci P., Berte C., Barras E., Fey S., Mach B. MHC class II regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domain. Genes Dev. 1990 Sep;4(9):1528–1540. doi: 10.1101/gad.4.9.1528. [DOI] [PubMed] [Google Scholar]
  28. Seto E., Lewis B., Shenk T. Interaction between transcription factors Sp1 and YY1. Nature. 1993 Sep 30;365(6445):462–464. doi: 10.1038/365462a0. [DOI] [PubMed] [Google Scholar]
  29. Seto E., Shi Y., Shenk T. YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991 Nov 21;354(6350):241–245. doi: 10.1038/354241a0. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Shipman-Appasamy P. M., Cohen K. S., Prystowsky M. B. Nucleotide sequence of murine PCNA: interspecies comparison of the cDNA and the 5' flanking region of the gene. DNA Seq. 1991;2(3):181–191. doi: 10.3109/10425179109039688. [DOI] [PubMed] [Google Scholar]
  32. Shivji K. K., Kenny M. K., Wood R. D. Proliferating cell nuclear antigen is required for DNA excision repair. Cell. 1992 Apr 17;69(2):367–374. doi: 10.1016/0092-8674(92)90416-a. [DOI] [PubMed] [Google Scholar]
  33. Shrivastava A., Saleque S., Kalpana G. V., Artandi S., Goff S. P., Calame K. Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc. Science. 1993 Dec 17;262(5141):1889–1892. doi: 10.1126/science.8266081. [DOI] [PubMed] [Google Scholar]
  34. Siegrist C. A., Durand B., Emery P., David E., Hearing P., Mach B., Reith W. RFX1 is identical to enhancer factor C and functions as a transactivator of the hepatitis B virus enhancer. Mol Cell Biol. 1993 Oct;13(10):6375–6384. doi: 10.1128/mcb.13.10.6375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stein R. W., Corrigan M., Yaciuk P., Whelan J., Moran E. Analysis of E1A-mediated growth regulation functions: binding of the 300-kilodalton cellular product correlates with E1A enhancer repression function and DNA synthesis-inducing activity. J Virol. 1990 Sep;64(9):4421–4427. doi: 10.1128/jvi.64.9.4421-4427.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Usheva A., Shenk T. TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA. Cell. 1994 Mar 25;76(6):1115–1121. doi: 10.1016/0092-8674(94)90387-5. [DOI] [PubMed] [Google Scholar]
  37. Waga S., Hannon G. J., Beach D., Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994 Jun 16;369(6481):574–578. doi: 10.1038/369574a0. [DOI] [PubMed] [Google Scholar]
  38. Waga S., Stillman B. Anatomy of a DNA replication fork revealed by reconstitution of SV40 DNA replication in vitro. Nature. 1994 May 19;369(6477):207–212. doi: 10.1038/369207a0. [DOI] [PubMed] [Google Scholar]
  39. Welch P. J., Wang J. Y. A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle. Cell. 1993 Nov 19;75(4):779–790. doi: 10.1016/0092-8674(93)90497-e. [DOI] [PubMed] [Google Scholar]
  40. Xiong Y., Hannon G. J., Zhang H., Casso D., Kobayashi R., Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701–704. doi: 10.1038/366701a0. [DOI] [PubMed] [Google Scholar]
  41. Xiong Y., Zhang H., Beach D. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell. 1992 Oct 30;71(3):505–514. doi: 10.1016/0092-8674(92)90518-h. [DOI] [PubMed] [Google Scholar]
  42. Xiong Y., Zhang H., Beach D. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev. 1993 Aug;7(8):1572–1583. doi: 10.1101/gad.7.8.1572. [DOI] [PubMed] [Google Scholar]
  43. Yoshimura T., Fujisawa J., Yoshida M. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. EMBO J. 1990 Aug;9(8):2537–2542. doi: 10.1002/j.1460-2075.1990.tb07434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zerler B., Roberts R. J., Mathews M. B., Moran E. Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products. Mol Cell Biol. 1987 Feb;7(2):821–829. doi: 10.1128/mcb.7.2.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zhang H., Xiong Y., Beach D. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell. 1993 Sep;4(9):897–906. doi: 10.1091/mbc.4.9.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zhu L., van den Heuvel S., Helin K., Fattaey A., Ewen M., Livingston D., Dyson N., Harlow E. Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes Dev. 1993 Jul;7(7A):1111–1125. doi: 10.1101/gad.7.7a.1111. [DOI] [PubMed] [Google Scholar]
  47. 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]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES