Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes (original) (raw)

Abstract

Although a number of transfection experiments have suggested potential targets for the action of the E2F1 transcription factor, as is the case for many transcriptional regulatory proteins, the actual targets in their normal chromosomal environment have not been demonstrated. We have made use of a recombinant adenovirus containing the E2F1 cDNA to infect quiescent cells and then measure the activation of endogenous cellular genes as a consequence of E2F1 production. We find that many of the genes encoding S-phase-acting proteins previously suspected to be E2F targets, including DNA polymerase alpha, thymidylate synthase, proliferating cell nuclear antigen, and ribonucleotide reductase, are indeed induced by E2F1. Several other candidates, including the dihydrofolate reductase and thymidine kinase genes, were only minimally induced by E2F1. In addition to the S-phase genes, we also find that several genes believed to play regulatory roles in cell cycle progression, such as the cdc2, cyclin A, and B-myb genes, are also induced by E2F1. Moreover, the cyclin E gene is strongly induced by E2F1, thus defining an autoregulatory circuit since cyclin E-dependent kinase activity can stimulate E2F1 transcription, likely through the phosphorylation and inactivation of Rb and Rb family members. Finally, we also demonstrate that a G1 arrest brought about by gamma irradiation is overcome by the overexpression of E2F1 and that this coincides with the enhanced activation of key target genes, including the cyclin A and cyclin E genes.

Full Text

The Full Text of this article is available as a PDF (939.5 KB).

Selected References

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

  1. Andrews B. J., Herskowitz I. Regulation of cell cycle-dependent gene expression in yeast. J Biol Chem. 1990 Aug 25;265(24):14057–14060. [PubMed] [Google Scholar]
  2. Bagchi S., Raychaudhuri P., Nevins J. R. 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. doi: 10.1016/0092-8674(90)90112-r. [DOI] [PubMed] [Google Scholar]
  3. Beijersbergen R. L., Kerkhoven R. M., Zhu L., Carlée L., Voorhoeve P. M., Bernards R. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes Dev. 1994 Nov 15;8(22):2680–2690. doi: 10.1101/gad.8.22.2680. [DOI] [PubMed] [Google Scholar]
  4. Björklund S., Hjortsberg K., Johansson E., Thelander L. Structure and promoter characterization of the gene encoding the large subunit (R1 protein) of mouse ribonucleotide reductase. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11322–11326. doi: 10.1073/pnas.90.23.11322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blake M. C., Azizkhan J. C. Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. Mol Cell Biol. 1989 Nov;9(11):4994–5002. doi: 10.1128/mcb.9.11.4994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Dalton S. Cell cycle regulation of the human cdc2 gene. EMBO J. 1992 May;11(5):1797–1804. doi: 10.1002/j.1460-2075.1992.tb05231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dimri G. P., Hara E., Campisi J. Regulation of two E2F-related genes in presenescent and senescent human fibroblasts. J Biol Chem. 1994 Jun 10;269(23):16180–16186. [PubMed] [Google Scholar]
  9. Dirick L., Moll T., Auer H., Nasmyth K. A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast. Nature. 1992 Jun 11;357(6378):508–513. doi: 10.1038/357508a0. [DOI] [PubMed] [Google Scholar]
  10. Dulić V., Kaufmann W. K., Wilson S. J., Tlsty T. D., Lees E., Harper J. W., Elledge S. J., Reed S. I. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell. 1994 Mar 25;76(6):1013–1023. doi: 10.1016/0092-8674(94)90379-4. [DOI] [PubMed] [Google Scholar]
  11. Fridovich-Keil J. L., Markell P. J., Gudas J. M., Pardee A. B. DNA sequences required for serum-responsive regulation of expression from the mouse thymidine kinase promoter. Cell Growth Differ. 1993 Aug;4(8):679–687. [PubMed] [Google Scholar]
  12. Ginsberg D., Vairo G., Chittenden T., Xiao Z. X., Xu G., Wydner K. L., DeCaprio J. A., Lawrence J. B., Livingston D. M. E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes Dev. 1994 Nov 15;8(22):2665–2679. doi: 10.1101/gad.8.22.2665. [DOI] [PubMed] [Google Scholar]
  13. Girard F., Strausfeld U., Fernandez A., Lamb N. J. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell. 1991 Dec 20;67(6):1169–1179. doi: 10.1016/0092-8674(91)90293-8. [DOI] [PubMed] [Google Scholar]
  14. Girling R., Partridge J. F., Bandara L. R., Burden N., Totty N. F., Hsuan J. J., La Thangue N. B. A new component of the transcription factor DRTF1/E2F. Nature. 1993 Mar 4;362(6415):83–87. doi: 10.1038/362083a0. [DOI] [PubMed] [Google Scholar]
  15. Gordon C. B., Campbell J. L. A cell cycle-responsive transcriptional control element and a negative control element in the gene encoding DNA polymerase alpha in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6058–6062. doi: 10.1073/pnas.88.14.6058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hara E., Okamoto S., Nakada S., Taya Y., Sekiya S., Oda K. Protein phosphorylation required for the formation of E2F complexes regulates N-myc transcription during differentiation of human embryonal carcinoma cells. Oncogene. 1993 Apr;8(4):1023–1032. [PubMed] [Google Scholar]
  17. Helin K., Lees J. A., Vidal M., Dyson N., Harlow E., Fattaey A. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell. 1992 Jul 24;70(2):337–350. doi: 10.1016/0092-8674(92)90107-n. [DOI] [PubMed] [Google Scholar]
  18. Henglein B., Chenivesse X., Wang J., Eick D., Bréchot C. Structure and cell cycle-regulated transcription of the human cyclin A gene. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5490–5494. doi: 10.1073/pnas.91.12.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hiebert S. W., Lipp M., Nevins J. R. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc Natl Acad Sci U S A. 1989 May;86(10):3594–3598. doi: 10.1073/pnas.86.10.3594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hiebert S. W. Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression. Mol Cell Biol. 1993 Jun;13(6):3384–3391. doi: 10.1128/mcb.13.6.3384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hsiao K. M., McMahon S. L., Farnham P. J. Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 1994 Jul 1;8(13):1526–1537. doi: 10.1101/gad.8.13.1526. [DOI] [PubMed] [Google Scholar]
  22. Hunter T. Braking the cycle. Cell. 1993 Dec 3;75(5):839–841. doi: 10.1016/0092-8674(93)90528-x. [DOI] [PubMed] [Google Scholar]
  23. Hunter T., Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994 Nov 18;79(4):573–582. doi: 10.1016/0092-8674(94)90543-6. [DOI] [PubMed] [Google Scholar]
  24. Ivey-Hoyle M., Conroy R., Huber H. E., Goodhart P. J., Oliff A., Heimbrook D. C. Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. Mol Cell Biol. 1993 Dec;13(12):7802–7812. doi: 10.1128/mcb.13.12.7802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Johnson D. G., Cress W. D., Jakoi L., Nevins J. R. Oncogenic capacity of the E2F1 gene. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12823–12827. doi: 10.1073/pnas.91.26.12823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Johnson D. G., Ohtani K., Nevins J. R. Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes Dev. 1994 Jul 1;8(13):1514–1525. doi: 10.1101/gad.8.13.1514. [DOI] [PubMed] [Google Scholar]
  27. Johnson D. G., Schwarz J. K., Cress W. D., Nevins J. R. Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature. 1993 Sep 23;365(6444):349–352. doi: 10.1038/365349a0. [DOI] [PubMed] [Google Scholar]
  28. Kaelin W. G., Jr, Krek W., Sellers W. R., DeCaprio J. A., Ajchenbaum F., Fuchs C. S., Chittenden T., Li Y., Farnham P. J., Blanar M. A. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell. 1992 Jul 24;70(2):351–364. doi: 10.1016/0092-8674(92)90108-o. [DOI] [PubMed] [Google Scholar]
  29. Kelly T. J., Martin G. S., Forsburg S. L., Stephen R. J., Russo A., Nurse P. The fission yeast cdc18+ gene product couples S phase to START and mitosis. Cell. 1993 Jul 30;74(2):371–382. doi: 10.1016/0092-8674(93)90427-r. [DOI] [PubMed] [Google Scholar]
  30. Kowalik T. F., DeGregori J., Schwarz J. K., Nevins J. R. E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. J Virol. 1995 Apr;69(4):2491–2500. doi: 10.1128/jvi.69.4.2491-2500.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. La Thangue N. B. DRTF1/E2F: an expanding family of heterodimeric transcription factors implicated in cell-cycle control. Trends Biochem Sci. 1994 Mar;19(3):108–114. doi: 10.1016/0968-0004(94)90202-x. [DOI] [PubMed] [Google Scholar]
  33. Lam E. W., Watson R. J. An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. EMBO J. 1993 Jul;12(7):2705–2713. doi: 10.1002/j.1460-2075.1993.tb05932.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lees J. A., Saito M., Vidal M., Valentine M., Look T., Harlow E., Dyson N., Helin K. The retinoblastoma protein binds to a family of E2F transcription factors. Mol Cell Biol. 1993 Dec;13(12):7813–7825. doi: 10.1128/mcb.13.12.7813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Li Y., Slansky J. E., Myers D. J., Drinkwater N. R., Kaelin W. G., Farnham P. J. Cloning, chromosomal location, and characterization of mouse E2F1. Mol Cell Biol. 1994 Mar;14(3):1861–1869. doi: 10.1128/mcb.14.3.1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lin D., Fiscella M., O'Connor P. M., Jackman J., Chen M., Luo L. L., Sala A., Travali S., Appella E., Mercer W. E. Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10079–10083. doi: 10.1073/pnas.91.21.10079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lowndes N. F., Johnson A. L., Johnston L. H. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature. 1991 Mar 21;350(6315):247–250. doi: 10.1038/350247a0. [DOI] [PubMed] [Google Scholar]
  38. Lowndes N. F., McInerny C. J., Johnson A. L., Fantes P. A., Johnston L. H. Control of DNA synthesis genes in fission yeast by the cell-cycle gene cdc10+. Nature. 1992 Jan 30;355(6359):449–453. doi: 10.1038/355449a0. [DOI] [PubMed] [Google Scholar]
  39. McIntosh E. M., Atkinson T., Storms R. K., Smith M. Characterization of a short, cis-acting DNA sequence which conveys cell cycle stage-dependent transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Jan;11(1):329–337. doi: 10.1128/mcb.11.1.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. McKinney J. D., Heintz N. Transcriptional regulation in the eukaryotic cell cycle. Trends Biochem Sci. 1991 Nov;16(11):430–435. doi: 10.1016/0968-0004(91)90170-z. [DOI] [PubMed] [Google Scholar]
  41. Means A. L., Slansky J. E., McMahon S. L., Knuth M. W., Farnham P. J. The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. Mol Cell Biol. 1992 Mar;12(3):1054–1063. doi: 10.1128/mcb.12.3.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Motokura T., Arnold A. PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes Chromosomes Cancer. 1993 Jun;7(2):89–95. doi: 10.1002/gcc.2870070205. [DOI] [PubMed] [Google Scholar]
  43. Mudryj M., Hiebert S. W., Nevins J. R. A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 1990 Jul;9(7):2179–2184. doi: 10.1002/j.1460-2075.1990.tb07387.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Müller H., Lukas J., Schneider A., Warthoe P., Bartek J., Eilers M., Strauss M. Cyclin D1 expression is regulated by the retinoblastoma protein. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2945–2949. doi: 10.1073/pnas.91.8.2945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Nasmyth K., Dirick L. The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast. Cell. 1991 Sep 6;66(5):995–1013. doi: 10.1016/0092-8674(91)90444-4. [DOI] [PubMed] [Google Scholar]
  46. Neuman E., Flemington E. K., Sellers W. R., Kaelin W. G., Jr Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. Mol Cell Biol. 1994 Oct;14(10):6607–6615. doi: 10.1128/mcb.14.10.6607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. Ogas J., Andrews B. J., Herskowitz I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell. 1991 Sep 6;66(5):1015–1026. doi: 10.1016/0092-8674(91)90445-5. [DOI] [PubMed] [Google Scholar]
  49. Oswald F., Lovec H., Möröy T., Lipp M. E2F-dependent regulation of human MYC: trans-activation by cyclins D1 and A overrides tumour suppressor protein functions. Oncogene. 1994 Jul;9(7):2029–2036. [PubMed] [Google Scholar]
  50. Pagano M., Pepperkok R., Verde F., Ansorge W., Draetta G. Cyclin A is required at two points in the human cell cycle. EMBO J. 1992 Mar;11(3):961–971. doi: 10.1002/j.1460-2075.1992.tb05135.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pagano M., Theodoras A. M., Tam S. W., Draetta G. F. Cyclin D1-mediated inhibition of repair and replicative DNA synthesis in human fibroblasts. Genes Dev. 1994 Jul 15;8(14):1627–1639. doi: 10.1101/gad.8.14.1627. [DOI] [PubMed] [Google Scholar]
  52. Pearson B. E., Nasheuer H. P., Wang T. S. Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells. Mol Cell Biol. 1991 Apr;11(4):2081–2095. doi: 10.1128/mcb.11.4.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Peter M., Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle. Cell. 1994 Oct 21;79(2):181–184. doi: 10.1016/0092-8674(94)90186-4. [DOI] [PubMed] [Google Scholar]
  54. Pizzagalli A., Valsasnini P., Plevani P., Lucchini G. DNA polymerase I gene of Saccharomyces cerevisiae: nucleotide sequence, mapping of a temperature-sensitive mutation, and protein homology with other DNA polymerases. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3772–3776. doi: 10.1073/pnas.85.11.3772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Qian Y., Luckey C., Horton L., Esser M., Templeton D. J. Biological function of the retinoblastoma protein requires distinct domains for hyperphosphorylation and transcription factor binding. Mol Cell Biol. 1992 Dec;12(12):5363–5372. doi: 10.1128/mcb.12.12.5363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Qin X. Q., Chittenden T., Livingston D. M., Kaelin W. G., Jr Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 1992 Jun;6(6):953–964. doi: 10.1101/gad.6.6.953. [DOI] [PubMed] [Google Scholar]
  57. Qin X. Q., Livingston D. M., Kaelin W. G., Jr, Adams P. D. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10918–10922. doi: 10.1073/pnas.91.23.10918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Roussel M. F., Davis J. N., Cleveland J. L., Ghysdael J., Hiebert S. W. Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1. Oncogene. 1994 Feb;9(2):405–415. [PubMed] [Google Scholar]
  59. Sala A., Calabretta B. Regulation of BALB/c 3T3 fibroblast proliferation by B-myb is accompanied by selective activation of cdc2 and cyclin D1 expression. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10415–10419. doi: 10.1073/pnas.89.21.10415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sala A., Nicolaides N. C., Engelhard A., Bellon T., Lawe D. C., Arnold A., Graña X., Giordano A., Calabretta B. Correlation between E2F-1 requirement in the S phase and E2F-1 transactivation of cell cycle-related genes in human cells. Cancer Res. 1994 Mar 15;54(6):1402–1406. [PubMed] [Google Scholar]
  61. Schwarz J. K., Bassing C. H., Kovesdi I., Datto M. B., Blazing M., George S., Wang X. F., Nevins J. R. Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):483–487. doi: 10.1073/pnas.92.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Shan B., Chang C. Y., Jones D., Lee W. H. The transcription factor E2F-1 mediates the autoregulation of RB gene expression. Mol Cell Biol. 1994 Jan;14(1):299–309. doi: 10.1128/mcb.14.1.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Shan B., Zhu X., Chen P. L., Durfee T., Yang Y., Sharp D., Lee W. H. Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F. Mol Cell Biol. 1992 Dec;12(12):5620–5631. doi: 10.1128/mcb.12.12.5620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sherr C. J. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. doi: 10.1016/0092-8674(94)90540-1. [DOI] [PubMed] [Google Scholar]
  65. Sherr C. J. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. doi: 10.1016/0092-8674(93)90636-5. [DOI] [PubMed] [Google Scholar]
  66. Singh P., Wong S. H., Hong W. Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation. EMBO J. 1994 Jul 15;13(14):3329–3338. doi: 10.1002/j.1460-2075.1994.tb06635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. 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]
  68. Thelander M., Thelander L. Molecular cloning and expression of the functional gene encoding the M2 subunit of mouse ribonucleotide reductase: a new dominant marker gene. EMBO J. 1989 Sep;8(9):2475–2479. doi: 10.1002/j.1460-2075.1989.tb08383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wang H. G., Rikitake Y., Carter M. C., Yaciuk P., Abraham S. E., Zerler B., Moran E. Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. J Virol. 1993 Jan;67(1):476–488. doi: 10.1128/jvi.67.1.476-488.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. 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]
  71. Wu X., Levine A. J. p53 and E2F-1 cooperate to mediate apoptosis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602–3606. doi: 10.1073/pnas.91.9.3602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Yamaguchi M., Hayashi Y., Hirose F., Matsuoka S., Shiroki K., Matsukage A. Activation of the mouse proliferating cell nuclear antigen gene promoter by adenovirus type 12 E1A proteins. Jpn J Cancer Res. 1992 Jun;83(6):609–617. doi: 10.1111/j.1349-7006.1992.tb00133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. el-Deiry W. S., Harper J. W., O'Connor P. M., Velculescu V. E., Canman C. E., Jackman J., Pietenpol J. A., Burrell M., Hill D. E., Wang Y. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 1994 Mar 1;54(5):1169–1174. [PubMed] [Google Scholar]