Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Aug;70(8):5373–5383. doi: 10.1128/jvi.70.8.5373-5383.1996

Importance of the Ser-132 phosphorylation site in cell transformation and apoptosis induced by the adenovirus type 5 E1A protein.

S G Whalen 1, R C Marcellus 1, D Barbeau 1, P E Branton 1
PMCID: PMC190495  PMID: 8764048

Abstract

The 289-residue (289R) and 243R early region 1A (E1A) proteins of human adenovirus type 5 induce cell transformation in cooperation with either E1B or activated ras. Here we report that Ser-132 in both E1A products is a site of phosphorylation in vivo and is the only site phosphorylated in vitro by purified casein kinase II. Ser-132 is located in conserved region 2 near the primary binding site for the pRB tumor suppressor and, in 289R, just upstream of the conserved region 3 transactivation domain involved in regulation of early viral gene expression. Mutants containing alanine or glycine in place of Ser-132 interacted with pRB-related proteins at somewhat reduced efficiency; however, all Ser-132 mutants transformed primary rat cells in cooperation with E1B as well as or better than the wild type when both major E1A proteins were expressed. Such was not the case with mutants expressing only 289R. In cooperation with E1B, the Asp-132 and Gly-132 mutants yielded reduced numbers of smaller transformed foci. With activated ras, all Ser-132 mutants were significantly defective for transformation and the rare foci produced were small and contained extensive areas populated by low densities of flat cells. In the absence of E1B, all Ser-132 mutants induced p53-independent cell death more readily than virus expressing wild-type 289R. These results suggested that phosphorylation at Ser-132 may enhance the binding of pRB and related proteins and also reduce the toxicity of E1A 289R, thus increasing transforming activity.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

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

  1. Barbeau D., Charbonneau R., Whalen S. G., Bayley S. T., Branton P. E. Functional interactions within adenovirus E1A protein complexes. Oncogene. 1994 Feb;9(2):359–373. [PubMed] [Google Scholar]
  2. Barbeau D., Marcellus R. C., Bacchetti S., Bayley S. T., Branton P. E. Quantitative analysis of regions of adenovirus E1A products involved in interactions with cellular proteins. Biochem Cell Biol. 1992 Oct-Nov;70(10-11):1123–1134. doi: 10.1139/o92-158. [DOI] [PubMed] [Google Scholar]
  3. Barbosa M. S., Edmonds C., Fisher C., Schiller J. T., Lowy D. R., Vousden K. H. The region of the HPV E7 oncoprotein homologous to adenovirus E1a and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation. EMBO J. 1990 Jan;9(1):153–160. doi: 10.1002/j.1460-2075.1990.tb08091.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berk A. J., Sharp P. A. Structure of the adenovirus 2 early mRNAs. Cell. 1978 Jul;14(3):695–711. doi: 10.1016/0092-8674(78)90252-0. [DOI] [PubMed] [Google Scholar]
  5. Carroll D., Santoro N., Marshak D. R. Regulating cell growth: casein-kinase-II-dependent phosphorylation of nuclear oncoproteins. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 1):91–95. doi: 10.1101/sqb.1988.053.01.014. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Colby W. W., Shenk T. Adenovirus type 5 virions can be assembled in vivo in the absence of detectable polypeptide IX. J Virol. 1981 Sep;39(3):977–980. doi: 10.1128/jvi.39.3.977-980.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Corbeil H. B., Branton P. E. Functional importance of complex formation between the retinoblastoma tumor suppressor family and adenovirus E1A proteins as determined by mutational analysis of E1A conserved region 2. J Virol. 1994 Oct;68(10):6697–6709. doi: 10.1128/jvi.68.10.6697-6709.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Debbas M., White E. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev. 1993 Apr;7(4):546–554. doi: 10.1101/gad.7.4.546. [DOI] [PubMed] [Google Scholar]
  10. Dumont D. J., Branton P. E. Phosphorylation of adenovirus E1A proteins by the p34cdc2 protein kinase. Virology. 1992 Jul;189(1):111–120. doi: 10.1016/0042-6822(92)90686-j. [DOI] [PubMed] [Google Scholar]
  11. Dumont D. J., Marcellus R. C., Bayley S. T., Branton P. E. Role of phosphorylation near the amino terminus of adenovirus type 5 early region 1A proteins. J Gen Virol. 1993 Apr;74(Pt 4):583–595. doi: 10.1099/0022-1317-74-4-583. [DOI] [PubMed] [Google Scholar]
  12. Dumont D. J., Tremblay M. L., Branton P. E. Phosphorylation at serine 89 induces a shift in gel mobility but has little effect on the function of adenovirus type 5 E1A proteins. J Virol. 1989 Feb;63(2):987–991. doi: 10.1128/jvi.63.2.987-991.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dyson N., Bernards R., Friend S. H., Gooding L. R., Hassell J. A., Major E. O., Pipas J. M., Vandyke T., Harlow E. Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol. 1990 Mar;64(3):1353–1356. doi: 10.1128/jvi.64.3.1353-1356.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  17. Egan C., Yee S. P., Ferguson B., Rosenberg M., Branton P. E. Binding of cellular polypeptides to human adenovirus type 5 E1A proteins produced in Escherichia coli. Virology. 1987 Sep;160(1):292–296. doi: 10.1016/0042-6822(87)90077-8. [DOI] [PubMed] [Google Scholar]
  18. Ewen M. E., Xing Y. G., Lawrence J. B., Livingston D. M. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell. 1991 Sep 20;66(6):1155–1164. doi: 10.1016/0092-8674(91)90038-z. [DOI] [PubMed] [Google Scholar]
  19. Faha B., Harlow E., Lees E. The adenovirus E1A-associated kinase consists of cyclin E-p33cdk2 and cyclin A-p33cdk2. J Virol. 1993 May;67(5):2456–2465. doi: 10.1128/jvi.67.5.2456-2465.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ferguson B., Jones N., Richter J., Rosenberg M. Adenovirus E1a gene product expressed at high levels in Escherichia coli is functional. Science. 1984 Jun 22;224(4655):1343–1346. doi: 10.1126/science.6374895. [DOI] [PubMed] [Google Scholar]
  21. Firzlaff J. M., Galloway D. A., Eisenman R. N., Lüscher B. The E7 protein of human papillomavirus type 16 is phosphorylated by casein kinase II. New Biol. 1989 Oct;1(1):44–53. [PubMed] [Google Scholar]
  22. Firzlaff J. M., Lüscher B., Eisenman R. N. Negative charge at the casein kinase II phosphorylation site is important for transformation but not for Rb protein binding by the E7 protein of human papillomavirus type 16. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5187–5191. doi: 10.1073/pnas.88.12.5187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  26. Graham F. L., van der Eb A. J., Heijneker H. L. Size and location of the transforming region in human adenovirus type 5 DNA. Nature. 1974 Oct 25;251(5477):687–691. doi: 10.1038/251687a0. [DOI] [PubMed] [Google Scholar]
  27. Haley K. P., Overhauser J., Babiss L. E., Ginsberg H. S., Jones N. C. Transformation properties of type 5 adenovirus mutants that differentially express the E1A gene products. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5734–5738. doi: 10.1073/pnas.81.18.5734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Harlow E., Whyte P., Franza B. R., Jr, Schley C. Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol Cell Biol. 1986 May;6(5):1579–1589. doi: 10.1128/mcb.6.5.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Harter M. L., Lewis J. B. Adenovirus type 2 early proteins synthesized in vitro and in vivo: identification in infected cells of the 38,000- to 50,000- molecular-weight protein encoded by the left end of the adenovirus type 2 genome. J Virol. 1978 Jun;26(3):736–749. doi: 10.1128/jvi.26.3.736-749.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Harvey D. M., Levine A. J. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev. 1991 Dec;5(12B):2375–2385. doi: 10.1101/gad.5.12b.2375. [DOI] [PubMed] [Google Scholar]
  32. Hateboer G., Timmers H. T., Rustgi A. K., Billaud M., van 't Veer L. J., Bernards R. TATA-binding protein and the retinoblastoma gene product bind to overlapping epitopes on c-Myc and adenovirus E1A protein. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8489–8493. doi: 10.1073/pnas.90.18.8489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Heck D. V., Yee C. L., Howley P. M., Münger K. Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4442–4446. doi: 10.1073/pnas.89.10.4442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Jelsma T. N., Howe J. A., Evelegh C. M., Cunniff N. F., Skiadopoulos M. H., Floroff M. R., Denman J. E., Bayley S. T. Use of deletion and point mutants spanning the coding region of the adenovirus 5 E1A gene to define a domain that is essential for transcriptional activation. Virology. 1988 Apr;163(2):494–502. doi: 10.1016/0042-6822(88)90290-5. [DOI] [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. Jones N., Shenk T. Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell. 1979 Jul;17(3):683–689. doi: 10.1016/0092-8674(79)90275-7. [DOI] [PubMed] [Google Scholar]
  37. Kitchingman G. R., Westphal H. The structure of adenovirus 2 early nuclear and cytoplasmic RNAs. J Mol Biol. 1980 Feb 15;137(1):23–48. doi: 10.1016/0022-2836(80)90155-2. [DOI] [PubMed] [Google Scholar]
  38. Kuppuswamy M. N., Chinnadurai G. Relationship between the transforming and transcriptional regulatory functions of adenovirus 2 E1a oncogene. Virology. 1987 Jul;159(1):31–38. doi: 10.1016/0042-6822(87)90344-8. [DOI] [PubMed] [Google Scholar]
  39. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  40. Larose A., Dyson N., Sullivan M., Harlow E., Bastin M. Polyomavirus large T mutants affected in retinoblastoma protein binding are defective in immortalization. J Virol. 1991 May;65(5):2308–2313. doi: 10.1128/jvi.65.5.2308-2313.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
  42. Lee W. S., Kao C. C., Bryant G. O., Liu X., Berk A. J. Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell. 1991 Oct 18;67(2):365–376. doi: 10.1016/0092-8674(91)90188-5. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Lillie J. W., Loewenstein P. M., Green M. R., Green M. Functional domains of adenovirus type 5 E1a proteins. Cell. 1987 Sep 25;50(7):1091–1100. doi: 10.1016/0092-8674(87)90175-9. [DOI] [PubMed] [Google Scholar]
  45. Liu F., Green M. R. Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains. Nature. 1994 Apr 7;368(6471):520–525. doi: 10.1038/368520a0. [DOI] [PubMed] [Google Scholar]
  46. Lowe S. W., Ruley H. E. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev. 1993 Apr;7(4):535–545. doi: 10.1101/gad.7.4.535. [DOI] [PubMed] [Google Scholar]
  47. McGrory W. J., Bautista D. S., Graham F. L. A simple technique for the rescue of early region I mutations into infectious human adenovirus type 5. Virology. 1988 Apr;163(2):614–617. doi: 10.1016/0042-6822(88)90302-9. [DOI] [PubMed] [Google Scholar]
  48. McKinnon R. D., Bacchetti S., Graham F. L. Tn5 mutagenesis of the transforming genes of human adenovirus type 5. Gene. 1982 Jul-Aug;19(1):33–42. doi: 10.1016/0378-1119(82)90186-x. [DOI] [PubMed] [Google Scholar]
  49. McLorie W., McGlade C. J., Takayesu D., Branton P. E. Individual adenovirus E1B proteins induce transformation independently but by additive pathways. J Gen Virol. 1991 Jun;72(Pt 6):1467–1471. doi: 10.1099/0022-1317-72-6-1467. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Montell C., Fisher E. F., Caruthers M. H., Berk A. J. Resolving the functions of overlapping viral genes by site-specific mutagenesis at a mRNA splice site. Nature. 1982 Feb 4;295(5848):380–384. doi: 10.1038/295380a0. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Mymryk J. S., Shire K., Bayley S. T. Induction of apoptosis by adenovirus type 5 E1A in rat cells requires a proliferation block. Oncogene. 1994 Apr;9(4):1187–1193. [PubMed] [Google Scholar]
  54. Münger K., Werness B. A., Dyson N., Phelps W. C., Harlow E., Howley P. M. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J. 1989 Dec 20;8(13):4099–4105. doi: 10.1002/j.1460-2075.1989.tb08594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Pearson R. B., Kemp B. E. Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol. 1991;200:62–81. doi: 10.1016/0076-6879(91)00127-i. [DOI] [PubMed] [Google Scholar]
  56. Perricaudet M., Akusjärvi G., Virtanen A., Pettersson U. Structure of two spliced mRNAs from the transforming region of human subgroup C adenoviruses. Nature. 1979 Oct 25;281(5733):694–696. doi: 10.1038/281694a0. [DOI] [PubMed] [Google Scholar]
  57. Phelps W. C., Münger K., Yee C. L., Barnes J. A., Howley P. M. Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. J Virol. 1992 Apr;66(4):2418–2427. doi: 10.1128/jvi.66.4.2418-2427.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Pöpperl H., Featherstone M. S. An autoregulatory element of the murine Hox-4.2 gene. EMBO J. 1992 Oct;11(10):3673–3680. doi: 10.1002/j.1460-2075.1992.tb05452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rao L., Debbas M., Sabbatini P., Hockenbery D., Korsmeyer S., White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742–7746. doi: 10.1073/pnas.89.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Rowe D. T., Graham F. L., Branton P. E. Intracellular localization of adenovirus type 5 tumor antigens in productively infected cells. Virology. 1983 Sep;129(2):456–468. doi: 10.1016/0042-6822(83)90183-6. [DOI] [PubMed] [Google Scholar]
  61. 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]
  62. 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]
  63. Shepherd S. E., Howe J. A., Mymryk J. S., Bayley S. T. Induction of the cell cycle in baby rat kidney cells by adenovirus type 5 E1A in the absence of E1B and a possible influence of p53. J Virol. 1993 May;67(5):2944–2949. doi: 10.1128/jvi.67.5.2944-2949.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Subramanian T., Tarodi B., Chinnadurai G. p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: suppression by E1B 19K and Bcl-2 proteins. Cell Growth Differ. 1995 Feb;6(2):131–137. [PubMed] [Google Scholar]
  65. Svensson C., Bondesson M., Nyberg E., Linder S., Jones N., Akusjärvi G. Independent transformation activity by adenovirus-5 E1A-conserved regions 1 or 2 mutants. Virology. 1991 Jun;182(2):553–561. doi: 10.1016/0042-6822(91)90596-4. [DOI] [PubMed] [Google Scholar]
  66. Teodoro J. G., Shore G. C., Branton P. E. Adenovirus E1A proteins induce apoptosis by both p53-dependent and p53-independent mechanisms. Oncogene. 1995 Aug 3;11(3):467–474. [PubMed] [Google Scholar]
  67. Tremblay M. L., Dumont D. J., Branton P. E. Analysis of phosphorylation sites in the exon 1 region of E1A proteins of human adenovirus type 5. Virology. 1989 Apr;169(2):397–407. doi: 10.1016/0042-6822(89)90165-7. [DOI] [PubMed] [Google Scholar]
  68. Tremblay M. L., McGlade C. J., Gerber G. E., Branton P. E. Identification of the phosphorylation sites in early region 1A proteins of adenovirus type 5 by amino acid sequencing of peptide fragments. J Biol Chem. 1988 May 5;263(13):6375–6383. [PubMed] [Google Scholar]
  69. Tsukamoto A. S., Ponticelli A., Berk A. J., Gaynor R. B. Genetic mapping of a major site of phosphorylation in adenovirus type 2 E1A proteins. J Virol. 1986 Jul;59(1):14–22. doi: 10.1128/jvi.59.1.14-22.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. 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]
  71. Webster L. C., Ricciardi R. P. trans-dominant mutants of E1A provide genetic evidence that the zinc finger of the trans-activating domain binds a transcription factor. Mol Cell Biol. 1991 Sep;11(9):4287–4296. doi: 10.1128/mcb.11.9.4287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Weeks D. L., Jones N. C. 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. doi: 10.1128/mcb.3.7.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. White E., Cipriani R., Sabbatini P., Denton A. Adenovirus E1B 19-kilodalton protein overcomes the cytotoxicity of E1A proteins. J Virol. 1991 Jun;65(6):2968–2978. doi: 10.1128/jvi.65.6.2968-2978.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. 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]
  75. Whyte P., Ruley H. E., Harlow E. Two regions of the adenovirus early region 1A proteins are required for transformation. J Virol. 1988 Jan;62(1):257–265. doi: 10.1128/jvi.62.1.257-265.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. 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]
  77. Yee S. P., Branton P. E. Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology. 1985 Nov;147(1):142–153. doi: 10.1016/0042-6822(85)90234-x. [DOI] [PubMed] [Google Scholar]
  78. Yee S. P., Rowe D. T., Tremblay M. L., McDermott M., Branton P. E. Identification of human adenovirus early region 1 products by using antisera against synthetic peptides corresponding to the predicted carboxy termini. J Virol. 1983 Jun;46(3):1003–1013. doi: 10.1128/jvi.46.3.1003-1013.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES