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J Virol. 1991 December; 65(12): 6397–6406.
PMCID: PMC250676
The adenovirus E1A transforming protein activates the proliferating cell nuclear antigen promoter via an activating transcription factor site.
G F Morris and M B Mathews
Cold Spring Harbor Laboratory, New York 11724.
Abstract
The transforming region of adenovirus (E1) stimulates expression of a reporter construct linked to the promoter for the human proliferating cell nuclear antigen (PCNA) gene in a cotransfection assay (G. F. Morris and M. B. Mathews, J. Biol. Chem. 264:13856-13864, 1989). The major products of the E1 region were assessed individually for their contribution to transactivation of the PCNA promoter. The E1A 13S and 12S products and the E1B 19-kDa product elevated expression from the PCNA promoter, whereas the E1B 55-kDa product did not. Induction of the PCNA promoter by E1A differed from transcriptional activation of the adenovirus E3 promoter in that the PCNA promoter is activated by the E1A 12S product whereas the E3 promoter is repressed; furthermore, the PCNA promoter is activated upon E1A overexpression, whereas the E3 promoter responds less well to high amounts of E1A. A site for the activating transcription factor ATF located approximately 50 nucleotides upstream from the transcription initiation site in the PCNA promoter mediates a positive response to the E1A 12S and 13S products.
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  • Adami, GR; Babiss, LE. The efficiency of adenovirus transformation of rodent cells is inversely related to the rate of viral E1A gene expression. J Virol. 1990 Jul;64(7):3427–3436. [PubMed]
  • Almendral, JM; Huebsch, D; Blundell, PA; Macdonald-Bravo, H; Bravo, R. Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1575–1579. [PubMed]
  • Bagchi, S; Raychaudhuri, P; Nevins, JR. Adenovirus E1A proteins can dissociate heteromeric complexes involving the E2F transcription factor: a novel mechanism for E1A trans-activation. Cell. 1990 Aug 24;62(4):659–669. [PubMed]
  • Barker, DD; Berk, AJ. Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection. Virology. 1987 Jan;156(1):107–121. [PubMed]
  • Bauer, GA; Burgers, PM. Molecular cloning, structure and expression of the yeast proliferating cell nuclear antigen gene. Nucleic Acids Res. 1990 Jan 25;18(2):261–265. [PubMed]
  • Benbrook, DM; Jones, NC. Heterodimer formation between CREB and JUN proteins. Oncogene. 1990 Mar;5(3):295–302. [PubMed]
  • Berk, AJ. Adenovirus promoters and E1A transactivation. Annu Rev Genet. 1986;20:45–79. [PubMed]
  • Bravo, R; Fey, SJ; Bellatin, J; Larsen, PM; Arevalo, J; Celis, JE. Identification of a nuclear and of a cytoplasmic polypeptide whose relative proportions are sensitive to changes in the rate of cell proliferation. Exp Cell Res. 1981 Dec;136(2):311–319. [PubMed]
  • Bravo, R; Frank, R; Blundell, PA; Macdonald-Bravo, H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 326(6112):515–517. [PubMed]
  • Brunet, LJ; Berk, AJ. Concentration dependence of transcriptional transactivation in inducible E1A-containing human cells. Mol Cell Biol. 1988 Nov;8(11):4799–4807. [PubMed]
  • Chang, CD; Ottavio, L; Travali, S; Lipson, KE; Baserga, R. Transcriptional and posttranscriptional regulation of the proliferating cell nuclear antigen gene. Mol Cell Biol. 1990 Jul;10(7):3289–3296. [PubMed]
  • de Groot, R; Foulkes, N; Mulder, M; Kruijer, W; Sassone-Corsi, P. Positive regulation of jun/AP-1 by E1A. Mol Cell Biol. 1991 Jan;11(1):192–201. [PubMed]
  • Dery, CV; Herrmann, CH; Mathews, MB. Response of individual adenovirus promoters to the products of the E1A gene. Oncogene. 1987;2(1):15–23. [PubMed]
  • Draetta, G; Beach, D; Moran, E. Synthesis of p34, the mammalian homolog of the yeast cdc2+/CDC28 protein kinase, is stimulated during adenovirus-induced proliferation of primary baby rat kidney cells. Oncogene. 1988 Jun;2(6):553–557. [PubMed]
  • Dyson, N; Howley, PM; Münger, K; Harlow, E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934–937. [PubMed]
  • Fahnestock, ML; Lewis, JB. Genetic dissection of the transactivating domain of the E1a 289R protein of adenovirus type 2. J Virol. 1989 Apr;63(4):1495–1504. [PubMed]
  • Flint, J; Shenk, T. Adenovirus E1A protein paradigm viral transactivator. Annu Rev Genet. 1989;23:141–161. [PubMed]
  • Garrels, JI; Franza, BR., Jr The REF52 protein database. Methods of database construction and analysis using the QUEST system and characterizations of protein patterns from proliferating and quiescent REF52 cells. J Biol Chem. 1989 Mar 25;264(9):5283–5298. [PubMed]
  • Garrels, JI; Franza, BR., Jr Transformation-sensitive and growth-related changes of protein synthesis in REF52 cells. A two-dimensional gel analysis of SV40-, adenovirus-, and Kirsten murine sarcoma virus-transformed rat cells using the REF52 protein database. J Biol Chem. 1989 Mar 25;264(9):5299–5312. [PubMed]
  • Glenn, GM; Ricciardi, RP. Detailed kinetics of adenovirus type-5 steady-state transcripts during early infection. Virus Res. 1988 Jan;9(1):73–91. [PubMed]
  • Gorman, CM; Gies, D; McCray, G; Huang, M. The human cytomegalovirus major immediate early promoter can be trans-activated by adenovirus early proteins. Virology. 1989 Aug;171(2):377–385. [PubMed]
  • Gorman, CM; Moffat, LF; Howard, BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PubMed]
  • Hai, TW; Liu, F; Coukos, WJ; Green, MR. 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. [PubMed]
  • Hardy, S; Engel, DA; Shenk, T. An adenovirus early region 4 gene product is required for induction of the infection-specific form of cellular E2F activity. Genes Dev. 1989 Jul;3(7):1062–1074. [PubMed]
  • Harlow, E; Whyte, P; Franza, BR, Jr; Schley, C. Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol Cell Biol. 1986 May;6(5):1579–1589. [PubMed]
  • Hen, R; Borrelli, E; Sassone-Corsi, P; Chambon, P. An enhancer element is located 340 base pairs upstream from the adenovirus-2 E1A capsite. Nucleic Acids Res. 1983 Dec 20;11(24):8747–8760. [PubMed]
  • Herrmann, CH; Dery, CV; Mathews, MB. Transactivation of host and viral genes by the adenovirus E1B 19K tumor antigen. Oncogene. 1987;2(1):25–35. [PubMed]
  • Herrmann, CH; Mathews, MB. The adenovirus E1B 19-kilodalton protein stimulates gene expression by increasing DNA levels. Mol Cell Biol. 1989 Dec;9(12):5412–5423. [PubMed]
  • Hitt, MM; Graham, FL. Adenovirus E1A under the control of heterologous promoters: wide variation in E1A expression levels has little effect on virus replication. Virology. 1990 Dec;179(2):667–678. [PubMed]
  • Horikoshi, M; Hai, T; Lin, YS; Green, MR; Roeder, RG. Transcription factor ATF interacts with the TATA factor to facilitate establishment of a preinitiation complex. Cell. 1988 Sep 23;54(7):1033–1042. [PubMed]
  • Howe, JA; Mymryk, JS; Egan, C; Branton, PE; Bayley, ST. 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. [PubMed]
  • Huang, MM; Hearing, P. Adenovirus early region 4 encodes two gene products with redundant effects in lytic infection. J Virol. 1989 Jun;63(6):2605–2615. [PubMed]
  • Jaskulski, D; deRiel, JK; Mercer, WE; Calabretta, B; Baserga, R. Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. Science. 1988 Jun 10;240(4858):1544–1546. [PubMed]
  • Jaskulski, D; Gatti, C; Travali, S; Calabretta, B; Baserga, R. Regulation of the proliferating cell nuclear antigen cyclin and thymidine kinase mRNA levels by growth factors. J Biol Chem. 1988 Jul 25;263(21):10175–10179. [PubMed]
  • Jelsma, TN; Howe, JA; Mymryk, JS; Evelegh, CM; Cunniff, NF; Bayley, ST. 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. [PubMed]
  • Jochemsen, AG; Peltenburg, LT; te Pas, MF; de Wit, CM; Bos, JL; van der Eb, AJ. Activation of adenovirus 5 E1A transcription by region E1B in transformed primary rat cells. EMBO J. 1987 Nov;6(11):3399–3405. [PubMed]
  • Jones, NC; Rigby, PW; Ziff, EB. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. [PubMed]
  • Kaddurah-Daouk, R; Lillie, JW; Daouk, GH; Green, MR; 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. [PubMed]
  • Kitabayashi, I; Chiu, R; Gachelin, G; Yokoyama, K. E1A dependent up-regulation of c-jun/AP-1 activity. Nucleic Acids Res. 1991 Feb 11;19(3):649–655. [PubMed]
  • Lee, KA; Hai, TY; SivaRaman, L; Thimmappaya, B; Hurst, HC; Jones, NC; Green, MR. A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355–8359. [PubMed]
  • Liu, F; Green, MR. 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. [PubMed]
  • Liu, YC; Marraccino, RL; Keng, PC; Bambara, RA; Lord, EM; Chou, WG; Zain, SB. Requirement for proliferating cell nuclear antigen expression during stages of the Chinese hamster ovary cell cycle. Biochemistry. 1989 Apr 4;28(7):2967–2974. [PubMed]
  • Martin, KJ; Lillie, JW; Green, MR. Evidence for interaction of different eukaryotic transcriptional activators with distinct cellular targets. Nature. 1990 Jul 12;346(6280):147–152. [PubMed]
  • Mathews, MB; Bernstein, RM; Franza, BR, Jr; Garrels, JI. Identity of the proliferating cell nuclear antigen and cyclin. Nature. 309(5966):374–376. [PubMed]
  • Matsumoto, K; Moriuchi, T; Koji, T; Nakane, PK. Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin. EMBO J. 1987 Mar;6(3):637–642. [PubMed]
  • Means, AL; Farnham, PJ. Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site. Mol Cell Biol. 1990 Feb;10(2):653–661. [PubMed]
  • Mercer, WE; Shields, MT; Lin, D; Appella, E; Ullrich, SJ. Growth suppression induced by wild-type p53 protein is accompanied by selective down-regulation of proliferating-cell nuclear antigen expression. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1958–1962. [PubMed]
  • Miyachi, K; Fritzler, MJ; Tan, EM. Autoantibody to a nuclear antigen in proliferating cells. J Immunol. 1978 Dec;121(6):2228–2234. [PubMed]
  • Moran, E; Mathews, MB. Multiple functional domains in the adenovirus E1A gene. Cell. 1987 Jan 30;48(2):177–178. [PubMed]
  • Morris, GF; Mathews, MB. Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem. 1989 Aug 15;264(23):13856–13864. [PubMed]
  • Morris, GF; Mathews, MB. Analysis of the proliferating cell nuclear antigen promoter and its response to adenovirus early region 1. J Biol Chem. 1990 Sep 25;265(27):16116–16125. [PubMed]
  • Mudryj, M; Hiebert, SW; Nevins, JR. A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 1990 Jul;9(7):2179–2184. [PubMed]
  • Müller, U; Roberts, MP; Engel, DA; Doerfler, W; Shenk, T. Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. Genes Dev. 1989 Dec;3(12A):1991–2002. [PubMed]
  • Nevins, JR. Mechanisms of viral-mediated trans-activation of transcription. Adv Virus Res. 1989;37:35–83. [PubMed]
  • Offringa, R; Gebel, S; van Dam, H; Timmers, M; Smits, A; Zwart, R; Stein, B; Bos, JL; van der Eb, A; Herrlich, P. A novel function of the transforming domain of E1a: repression of AP-1 activity. Cell. 1990 Aug 10;62(3):527–538. [PubMed]
  • Parks, CL; Spector, DJ. cis-dominant defect in activation of adenovirus type 5 E1b early RNA synthesis. J Virol. 1990 Jun;64(6):2780–2787. [PubMed]
  • Prelich, G; Kostura, M; Marshak, DR; Mathews, MB; 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. [PubMed]
  • Prelich, G; Tan, CK; Kostura, M; Mathews, MB; So, AG; Downey, KM; Stillman, B. Functional identity of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature. 326(6112):517–520. [PubMed]
  • Rochette-Egly, C; Fromental, C; Chambon, P. General repression of enhanson activity by the adenovirus-2 E1A proteins. Genes Dev. 1990 Jan;4(1):137–150. [PubMed]
  • Ruley, HE. Transforming collaborations between ras and nuclear oncogenes. Cancer Cells. 1990 2(8-9):258–268.Aug–Sep; [PubMed]
  • Senear, AW; Lewis, JB. Morphological transformation of established rodent cell lines by high-level expression of the adenovirus type 2 E1a gene. Mol Cell Biol. 1986 Apr;6(4):1253–1260. [PubMed]
  • Shiroki, K; Kato, H; Kawai, S. Tandemly repeated hexamer sequences within the beta interferon promoter can function as an inducible regulatory element in activation by the adenovirus E1B 19-kilodalton protein. J Virol. 1990 Jun;64(6):3063–3068. [PubMed]
  • Simon, MC; Kitchener, K; Kao, HT; Hickey, E; Weber, L; Voellmy, R; Heintz, N; Nevins, JR. 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. [PubMed]
  • Smale, ST; Baltimore, D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. [PubMed]
  • Tan, CK; Castillo, C; So, AG; Downey, KM. An auxiliary protein for DNA polymerase-delta from fetal calf thymus. J Biol Chem. 1986 Sep 15;261(26):12310–12316. [PubMed]
  • Taylor, IC; Kingston, RE. Factor substitution in a human HSP70 gene promoter: TATA-dependent and TATA-independent interactions. Mol Cell Biol. 1990 Jan;10(1):165–175. [PubMed]
  • Thomas, GP; Mathews, MB. DNA replication and the early to late transition in adenovirus infection. Cell. 1980 Nov;22(2 Pt 2):523–533. [PubMed]
  • van Dam, H; Offringa, R; Meijer, I; Stein, B; Smits, AM; Herrlich, P; Bos, JL; van der Eb, AJ. Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family. Mol Cell Biol. 1990 Nov;10(11):5857–5864. [PubMed]
  • Velcich, A; Ziff, E. Adenovirus E1a proteins repress transcription from the SV40 early promoter. Cell. 1985 Mar;40(3):705–716. [PubMed]
  • Weeks, DL; Jones, NC. E1A control of gene expression is mediated by sequences 5' to the transcriptional starts of the early viral genes. Mol Cell Biol. 1983 Jul;3(7):1222–1234. [PubMed]
  • Werness, BA; Levine, AJ; Howley, PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. [PubMed]
  • White, E; Cipriani, R. Role of adenovirus E1B proteins in transformation: altered organization of intermediate filaments in transformed cells that express the 19-kilodalton protein. Mol Cell Biol. 1990 Jan;10(1):120–130. [PubMed]
  • Widen, SG; Kedar, P; Wilson, SH. Human beta-polymerase gene. Structure of the 5'-flanking region and active promoter. J Biol Chem. 1988 Nov 15;263(32):16992–16998. [PubMed]
  • Yamaguchi, M; Hayashi, Y; Hirose, F; Matsuoka, S; Moriuchi, T; Shiroishi, T; Moriwaki, K; Matsukage, A. Molecular cloning and structural analysis of mouse gene and pseudogenes for proliferating cell nuclear antigen. Nucleic Acids Res. 1991 May 11;19(9):2403–2410. [PubMed]
  • Yee, SP; Branton, PE. Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology. 1985 Nov;147(1):142–153. [PubMed]
  • Yoshida, K; Venkatesh, L; Kuppuswamy, M; Chinnadurai, G. Adenovirus transforming 19-kD T antigen has an enhancer-dependent trans-activation function and relieves enhancer repression mediated by viral and cellular genes. Genes Dev. 1987 Sep;1(7):645–658. [PubMed]
  • Zerler, B; Moran, B; Maruyama, K; Moomaw, J; Grodzicker, T; Ruley, HE. Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells. Mol Cell Biol. 1986 Mar;6(3):887–899. [PubMed]
  • Zerler, B; Roberts, RJ; Mathews, MB; 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. [PubMed]