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. 1991 Aug;11(8):4253–4265. doi: 10.1128/mcb.11.8.4253

E1A induces phosphorylation of the retinoblastoma protein independently of direct physical association between the E1A and retinoblastoma products.

H G Wang 1, G Draetta 1, E Moran 1
PMCID: PMC361255  PMID: 1830128

Abstract

We have studied the initial effects of adenovirus E1A expression on the retinoblastoma (RB) gene product in normal quiescent cells. Although binding of the E1A products to pRB could, in theory, make pRB phosphorylation unnecessary for cell cycle progression, we have found that the 12S wild-type E1A product is capable of inducing phosphorylation of pRB in normal quiescent cells. The induction of pRB phosphorylation correlates with E1A-mediated induction of p34cdc2 expression and kinase activity, consistent with the possibility that p34cdc2 is a pRB kinase. Expression of simian virus 40 T antigen induces similar effects. Induction of pRB phosphorylation is independent of the pRB binding activity of the E1A products; E1A domain 2 mutants do not bind detectable levels of pRB but remain competent to induce pRB phosphorylation and to activate cdc2 protein kinase expression and activity. Although the kinetics of induction are slower, domain 2 mutants induce wild-type levels of pRB phosphorylation and host cell DNA synthesis and yet fail to induce cell proliferation. These results imply that direct physical interaction between the RB and E1A products does not play a required role in the early stages of E1A-mediated cell cycle induction and that pRB phosphorylation is not, of itself, sufficient to allow quiescent cells to divide. These results suggest that the E1A products do not need to bind pRB in order to stimulate resting cells to enter the cell cycle. Indeed, a more important role of the RB binding activity of the E1A products may be to prevent dividing cells from returning to G0.

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Selected References

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

  1. Arion D., Meijer L., Brizuela L., Beach D. cdc2 is a component of the M phase-specific histone H1 kinase: evidence for identity with MPF. Cell. 1988 Oct 21;55(2):371–378. doi: 10.1016/0092-8674(88)90060-8. [DOI] [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. Blow J. J., Nurse P. A cdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts. Cell. 1990 Sep 7;62(5):855–862. doi: 10.1016/0092-8674(90)90261-c. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Brizuela L., Draetta G., Beach D. Activation of human CDC2 protein as a histone H1 kinase is associated with complex formation with the p62 subunit. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4362–4366. doi: 10.1073/pnas.86.12.4362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brizuela L., Draetta G., Beach D. p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase. EMBO J. 1987 Nov;6(11):3507–3514. doi: 10.1002/j.1460-2075.1987.tb02676.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buchkovich K., Duffy L. A., Harlow E. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell. 1989 Sep 22;58(6):1097–1105. doi: 10.1016/0092-8674(89)90508-4. [DOI] [PubMed] [Google Scholar]
  8. Carlock L. R., Jones N. C. Transformation-defective mutant of adenovirus type 5 containing a single altered E1a mRNA species. J Virol. 1981 Dec;40(3):657–664. doi: 10.1128/jvi.40.3.657-664.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  10. Chen P. L., Scully P., Shew J. Y., Wang J. Y., Lee W. H. Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell. 1989 Sep 22;58(6):1193–1198. doi: 10.1016/0092-8674(89)90517-5. [DOI] [PubMed] [Google Scholar]
  11. Chow L. T., Broker T. R., Lewis J. B. Complex splicing patterns of RNAs from the early regions of adenovirus-2. J Mol Biol. 1979 Oct 25;134(2):265–303. doi: 10.1016/0022-2836(79)90036-6. [DOI] [PubMed] [Google Scholar]
  12. Cooper J. A., Whyte P. RB and the cell cycle: entrance or exit? Cell. 1989 Sep 22;58(6):1009–1011. doi: 10.1016/0092-8674(89)90495-9. [DOI] [PubMed] [Google Scholar]
  13. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988 Jul 15;54(2):275–283. doi: 10.1016/0092-8674(88)90559-4. [DOI] [PubMed] [Google Scholar]
  14. DeCaprio J. A., Ludlow J. W., Lynch D., Furukawa Y., Griffin J., Piwnica-Worms H., Huang C. M., Livingston D. M. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell. 1989 Sep 22;58(6):1085–1095. doi: 10.1016/0092-8674(89)90507-2. [DOI] [PubMed] [Google Scholar]
  15. Draetta G., Beach D. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. Cell. 1988 Jul 1;54(1):17–26. doi: 10.1016/0092-8674(88)90175-4. [DOI] [PubMed] [Google Scholar]
  16. 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] [Google Scholar]
  17. Draetta G., Brizuela L., Potashkin J., Beach D. Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+. Cell. 1987 Jul 17;50(2):319–325. doi: 10.1016/0092-8674(87)90227-3. [DOI] [PubMed] [Google Scholar]
  18. Draetta G. Cell cycle control in eukaryotes: molecular mechanisms of cdc2 activation. Trends Biochem Sci. 1990 Oct;15(10):378–383. doi: 10.1016/0968-0004(90)90235-4. [DOI] [PubMed] [Google Scholar]
  19. Draetta G., Piwnica-Worms H., Morrison D., Druker B., Roberts T., Beach D. Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrate. Nature. 1988 Dec 22;336(6201):738–744. doi: 10.1038/336738a0. [DOI] [PubMed] [Google Scholar]
  20. Dyson N., Howley P. M., 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. doi: 10.1126/science.2537532. [DOI] [PubMed] [Google Scholar]
  21. Egan C., Bayley S. T., Branton P. E. Binding of the Rb1 protein to E1A products is required for adenovirus transformation. Oncogene. 1989 Mar;4(3):383–388. [PubMed] [Google Scholar]
  22. Egan C., Jelsma T. N., Howe J. A., Bayley S. T., Ferguson B., Branton P. E. Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5. Mol Cell Biol. 1988 Sep;8(9):3955–3959. doi: 10.1128/mcb.8.9.3955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
  24. Friend S. H., Horowitz J. M., Gerber M. R., Wang X. F., Bogenmann E., Li F. P., Weinberg R. A. Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9059–9063. doi: 10.1073/pnas.84.24.9059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Fung Y. K., Murphree A. L., T'Ang A., Qian J., Hinrichs S. H., Benedict W. F. Structural evidence for the authenticity of the human retinoblastoma gene. Science. 1987 Jun 26;236(4809):1657–1661. doi: 10.1126/science.2885916. [DOI] [PubMed] [Google Scholar]
  26. Furukawa Y., DeCaprio J. A., Freedman A., Kanakura Y., Nakamura M., Ernst T. J., Livingston D. M., Griffin J. D. Expression and state of phosphorylation of the retinoblastoma susceptibility gene product in cycling and noncycling human hematopoietic cells. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2770–2774. doi: 10.1073/pnas.87.7.2770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Furukawa Y., Piwnica-Worms H., Ernst T. J., Kanakura Y., Griffin J. D. cdc2 gene expression at the G1 to S transition in human T lymphocytes. Science. 1990 Nov 9;250(4982):805–808. doi: 10.1126/science.2237430. [DOI] [PubMed] [Google Scholar]
  28. Giordano A., Whyte P., Harlow E., Franza B. R., Jr, Beach D., Draetta G. A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells. Cell. 1989 Sep 8;58(5):981–990. doi: 10.1016/0092-8674(89)90949-5. [DOI] [PubMed] [Google Scholar]
  29. Glenn G. M., Ricciardi R. P. Adenovirus 5 early region 1A host range mutants hr3, hr4, and hr5 contain point mutations which generate single amino acid substitutions. J Virol. 1985 Oct;56(1):66–74. doi: 10.1128/jvi.56.1.66-74.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  31. Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Harlow E., Franza B. R., Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. doi: 10.1128/jvi.55.3.533-546.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Houweling A., van den Elsen P. J., van der Eb A. J. Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA. Virology. 1980 Sep;105(2):537–550. doi: 10.1016/0042-6822(80)90054-9. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Langan T. A., Gautier J., Lohka M., Hollingsworth R., Moreno S., Nurse P., Maller J., Sclafani R. A. Mammalian growth-associated H1 histone kinase: a homolog of cdc2+/CDC28 protein kinases controlling mitotic entry in yeast and frog cells. Mol Cell Biol. 1989 Sep;9(9):3860–3868. doi: 10.1128/mcb.9.9.3860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lee E. Y., To H., Shew J. Y., Bookstein R., Scully P., Lee W. H. Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science. 1988 Jul 8;241(4862):218–221. doi: 10.1126/science.3388033. [DOI] [PubMed] [Google Scholar]
  39. Lee W. H., Bookstein R., Hong F., Young L. J., Shew J. Y., Lee E. Y. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science. 1987 Mar 13;235(4794):1394–1399. doi: 10.1126/science.3823889. [DOI] [PubMed] [Google Scholar]
  40. Lee W. H., Shew J. Y., Hong F. D., Sery T. W., Donoso L. A., Young L. J., Bookstein R., Lee E. Y. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature. 1987 Oct 15;329(6140):642–645. doi: 10.1038/329642a0. [DOI] [PubMed] [Google Scholar]
  41. Lillie J. W., Green M., Green M. R. An adenovirus E1a protein region required for transformation and transcriptional repression. Cell. 1986 Sep 26;46(7):1043–1051. doi: 10.1016/0092-8674(86)90704-x. [DOI] [PubMed] [Google Scholar]
  42. Lin B. T., Gruenwald S., Morla A. O., Lee W. H., Wang J. Y. Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase. EMBO J. 1991 Apr;10(4):857–864. doi: 10.1002/j.1460-2075.1991.tb08018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Ludlow J. W., DeCaprio J. A., Huang C. M., Lee W. H., Paucha E., Livingston D. M. SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family. Cell. 1989 Jan 13;56(1):57–65. doi: 10.1016/0092-8674(89)90983-5. [DOI] [PubMed] [Google Scholar]
  44. Ludlow J. W., Shon J., Pipas J. M., Livingston D. M., DeCaprio J. A. The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T. Cell. 1990 Feb 9;60(3):387–396. doi: 10.1016/0092-8674(90)90590-b. [DOI] [PubMed] [Google Scholar]
  45. Mihara K., Cao X. R., Yen A., Chandler S., Driscoll B., Murphree A. L., T'Ang A., Fung Y. K. Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. Science. 1989 Dec 8;246(4935):1300–1303. doi: 10.1126/science.2588006. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. Moran B., Zerler B. Interactions between cell growth-regulating domains in the products of the adenovirus E1A oncogene. Mol Cell Biol. 1988 Apr;8(4):1756–1764. doi: 10.1128/mcb.8.4.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Moran E. A region of SV40 large T antigen can substitute for a transforming domain of the adenovirus E1A products. Nature. 1988 Jul 14;334(6178):168–170. doi: 10.1038/334168a0. [DOI] [PubMed] [Google Scholar]
  49. Moran E., Grodzicker T., Roberts R. J., Mathews M. B., Zerler B. Lytic and transforming functions of individual products of the adenovirus E1A gene. J Virol. 1986 Mar;57(3):765–775. doi: 10.1128/jvi.57.3.765-775.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Moran E., Mathews M. B. Multiple functional domains in the adenovirus E1A gene. Cell. 1987 Jan 30;48(2):177–178. doi: 10.1016/0092-8674(87)90418-1. [DOI] [PubMed] [Google Scholar]
  51. Moran E., Zerler B., Harrison T. M., Mathews M. B. Identification of separate domains in the adenovirus E1A gene for immortalization activity and the activation of virus early genes. Mol Cell Biol. 1986 Oct;6(10):3470–3480. doi: 10.1128/mcb.6.10.3470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Nevins J. R. Mechanism of activation of early viral transcription by the adenovirus E1A gene product. Cell. 1981 Oct;26(2 Pt 2):213–220. doi: 10.1016/0092-8674(81)90304-4. [DOI] [PubMed] [Google Scholar]
  53. Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. doi: 10.1038/344503a0. [DOI] [PubMed] [Google Scholar]
  54. Offringa R., Gebel S., van Dam H., Timmers M., Smits A., Zwart R., Stein B., Bos J. L., 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. doi: 10.1016/0092-8674(90)90017-9. [DOI] [PubMed] [Google Scholar]
  55. Phelps W. C., Yee C. L., Münger K., Howley P. M. The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A. Cell. 1988 May 20;53(4):539–547. doi: 10.1016/0092-8674(88)90570-3. [DOI] [PubMed] [Google Scholar]
  56. Pietenpol J. A., Stein R. W., Moran E., Yaciuk P., Schlegel R., Lyons R. M., Pittelkow M. R., Münger K., Howley P. M., Moses H. L. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell. 1990 Jun 1;61(5):777–785. doi: 10.1016/0092-8674(90)90188-k. [DOI] [PubMed] [Google Scholar]
  57. Pines J., Hunter T. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B. Nature. 1990 Aug 23;346(6286):760–763. doi: 10.1038/346760a0. [DOI] [PubMed] [Google Scholar]
  58. Pines J., Hunter T. p34cdc2: the S and M kinase? New Biol. 1990 May;2(5):389–401. [PubMed] [Google Scholar]
  59. Quinlan M. P., Grodzicker T. Adenovirus E1A 12S protein induces DNA synthesis and proliferation in primary epithelial cells in both the presence and absence of serum. J Virol. 1987 Mar;61(3):673–682. doi: 10.1128/jvi.61.3.673-682.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Raychaudhuri P., Bagchi S., Devoto S. H., Kraus V. B., Moran E., Nevins J. R. Domains of the adenovirus E1A protein required for oncogenic activity are also required for dissociation of E2F transcription factor complexes. Genes Dev. 1991 Jul;5(7):1200–1211. doi: 10.1101/gad.5.7.1200. [DOI] [PubMed] [Google Scholar]
  61. Riabowol K., Draetta G., Brizuela L., Vandre D., Beach D. The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells. Cell. 1989 May 5;57(3):393–401. doi: 10.1016/0092-8674(89)90914-8. [DOI] [PubMed] [Google Scholar]
  62. Robbins P. D., Horowitz J. M., Mulligan R. C. Negative regulation of human c-fos expression by the retinoblastoma gene product. Nature. 1990 Aug 16;346(6285):668–671. doi: 10.1038/346668a0. [DOI] [PubMed] [Google Scholar]
  63. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  64. Schneider J. F., Fisher F., Goding C. R., Jones N. C. Mutational analysis of the adenovirus E1a gene: the role of transcriptional regulation in transformation. EMBO J. 1987 Jul;6(7):2053–2060. doi: 10.1002/j.1460-2075.1987.tb02470.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Smith D. H., Ziff E. B. The amino-terminal region of the adenovirus serotype 5 E1a protein performs two separate functions when expressed in primary baby rat kidney cells. Mol Cell Biol. 1988 Sep;8(9):3882–3890. doi: 10.1128/mcb.8.9.3882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. 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]
  67. Stephens C., Harlow E. Differential splicing yields novel adenovirus 5 E1A mRNAs that encode 30 kd and 35 kd proteins. EMBO J. 1987 Jul;6(7):2027–2035. doi: 10.1002/j.1460-2075.1987.tb02467.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Svensson C., Akusjärvi G. Adenovirus 2 early region 1A stimulates expression of both viral and cellular genes. EMBO J. 1984 Apr;3(4):789–794. doi: 10.1002/j.1460-2075.1984.tb01886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Taya Y., Yasuda H., Kamijo M., Nakaya K., Nakamura Y., Ohba Y., Nishimura S. In vitro phosphorylation of the tumor suppressor gene RB protein by mitosis-specific histone H1 kinase. Biochem Biophys Res Commun. 1989 Oct 16;164(1):580–586. doi: 10.1016/0006-291x(89)91759-2. [DOI] [PubMed] [Google Scholar]
  70. Ulfendahl P. J., Linder S., Kreivi J. P., Nordqvist K., Sevensson C., Hultberg H., Akusjärvi G. A novel adenovirus-2 E1A mRNA encoding a protein with transcription activation properties. EMBO J. 1987 Jul;6(7):2037–2044. doi: 10.1002/j.1460-2075.1987.tb02468.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Virtanen A., Pettersson U. The molecular structure of the 9S mRNA from early region 1A of adenovirus serotype 2. J Mol Biol. 1983 Apr 15;165(3):496–499. doi: 10.1016/s0022-2836(83)80215-0. [DOI] [PubMed] [Google Scholar]
  72. 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]
  73. Whyte P., Buchkovich K. J., Horowitz J. M., Friend S. H., Raybuck M., Weinberg R. A., Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. doi: 10.1038/334124a0. [DOI] [PubMed] [Google Scholar]
  74. 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]
  75. Xu H. J., Hu S. X., Hashimoto T., Takahashi R., Benedict W. F. The retinoblastoma susceptibility gene product: a characteristic pattern in normal cells and abnormal expression in malignant cells. Oncogene. 1989 Jun;4(6):807–812. [PubMed] [Google Scholar]
  76. Yaciuk P., Carter M. C., Pipas J. M., Moran E. Simian virus 40 large-T antigen expresses a biological activity complementary to the p300-associated transforming function of the adenovirus E1A gene products. Mol Cell Biol. 1991 Apr;11(4):2116–2124. doi: 10.1128/mcb.11.4.2116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. 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]
  78. 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]

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