Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Jun;68(6):3724–3732. doi: 10.1128/jvi.68.6.3724-3732.1994

Dissociation of retinoblastoma gene protein hyperphosphorylation and commitment to enter S phase.

V V Ogryzko 1, T H Hirai 1, C E Shih 1, B H Howard 1
PMCID: PMC236877  PMID: 8189510

Abstract

Mitogenic activities of simian virus 40 large T and small t antigens were studied in serum-deprived human diploid fibroblasts. Wild-type large T and small t cooperated in stimulating DNA synthesis and in inducing hyperphosphorylation of the Rb gene product (pRb). In contrast, a T antigen mutant defective for pRb binding (Rb- T) possessed no detectable mitogenic activity alone and failed to complement small t in stimulating DNA synthesis. Surprisingly, Rb- T and small t cooperated as strongly as wild-type T and small t with respect to pRb hyperphosphorylation. As a consequence, in two closely related conditions (i.e., stimulation by small t plus wild-type T versus small t plus Rb- T), the fraction of pRb in hyperphosphorylated forms dissociated from the fraction of cells in the S phase. These results indicate that pRb hyperphosphorylation is not always tightly coupled with a commitment to initiate DNA replication.

Full text

PDF
3732

Images in this article

3727Image
on p.3727
3727Image
on p.3727
3728Image
on p.3728
3729Image
on p.3729

Selected References

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

  1. Alberts A. S., Thorburn A. M., Shenolikar S., Mumby M. C., Feramisco J. R. Regulation of cell cycle progression and nuclear affinity of the retinoblastoma protein by protein phosphatases. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):388–392. doi: 10.1073/pnas.90.2.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bagchi S., Weinmann R., Raychaudhuri P. The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F. Cell. 1991 Jun 14;65(6):1063–1072. doi: 10.1016/0092-8674(91)90558-g. [DOI] [PubMed] [Google Scholar]
  3. Bandara L. R., Adamczewski J. P., Hunt T., La Thangue N. B. Cyclin A and the retinoblastoma gene product complex with a common transcription factor. Nature. 1991 Jul 18;352(6332):249–251. doi: 10.1038/352249a0. [DOI] [PubMed] [Google Scholar]
  4. Bikel I., Montano X., Agha M. E., Brown M., McCormack M., Boltax J., Livingston D. M. SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen. Cell. 1987 Jan 30;48(2):321–330. doi: 10.1016/0092-8674(87)90435-1. [DOI] [PubMed] [Google Scholar]
  5. Bookstein R., Shew J. Y., Chen P. L., Scully P., Lee W. H. Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science. 1990 Feb 9;247(4943):712–715. doi: 10.1126/science.2300823. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cavenee W. K., Hansen M. F., Nordenskjold M., Kock E., Maumenee I., Squire J. A., Phillips R. A., Gallie B. L. Genetic origin of mutations predisposing to retinoblastoma. Science. 1985 Apr 26;228(4698):501–503. doi: 10.1126/science.3983638. [DOI] [PubMed] [Google Scholar]
  8. Chang L. S., Pan S., Pater M. M., Di Mayorca G. Differential requirement for SV40 early genes in immortalization and transformation of primary rat and human embryonic cells. Virology. 1985 Oct 30;146(2):246–261. doi: 10.1016/0042-6822(85)90008-x. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Cherington V., Brown M., Paucha E., St Louis J., Spiegelman B. M., Roberts T. M. Separation of simian virus 40 large-T-antigen-transforming and origin-binding functions from the ability to block differentiation. Mol Cell Biol. 1988 Mar;8(3):1380–1384. doi: 10.1128/mcb.8.3.1380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DeCaprio J. A., Furukawa Y., Ajchenbaum F., Griffin J. D., Livingston D. M. The retinoblastoma-susceptibility gene product becomes phosphorylated in multiple stages during cell cycle entry and progression. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1795–1798. doi: 10.1073/pnas.89.5.1795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Dowdy S. F., Hinds P. W., Louie K., Reed S. I., Arnold A., Weinberg R. A. Physical interaction of the retinoblastoma protein with human D cyclins. Cell. 1993 May 7;73(3):499–511. doi: 10.1016/0092-8674(93)90137-f. [DOI] [PubMed] [Google Scholar]
  15. Durfee T., Becherer K., Chen P. L., Yeh S. H., Yang Y., Kilburn A. E., Lee W. H., Elledge S. J. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. doi: 10.1101/gad.7.4.555. [DOI] [PubMed] [Google Scholar]
  16. Dyson N., Buchkovich K., Whyte P., Harlow E. The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus. Cell. 1989 Jul 28;58(2):249–255. doi: 10.1016/0092-8674(89)90839-8. [DOI] [PubMed] [Google Scholar]
  17. Ewen M. E., Sluss H. K., Sherr C. J., Matsushime H., Kato J., Livingston D. M. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell. 1993 May 7;73(3):487–497. doi: 10.1016/0092-8674(93)90136-e. [DOI] [PubMed] [Google Scholar]
  18. Fanning E. Simian virus 40 large T antigen: the puzzle, the pieces, and the emerging picture. J Virol. 1992 Mar;66(3):1289–1293. doi: 10.1128/jvi.66.3.1289-1293.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fiers W., Contreras R., Haegemann G., Rogiers R., Van de Voorde A., Van Heuverswyn H., Van Herreweghe J., Volckaert G., Ysebaert M. Complete nucleotide sequence of SV40 DNA. Nature. 1978 May 11;273(5658):113–120. doi: 10.1038/273113a0. [DOI] [PubMed] [Google Scholar]
  20. Fordis C. M., Helmly B., Novotny E., Holter W., Barker J. L., Howard B. H. Transient analysis for antiproliferative gene activity. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1169–1173. doi: 10.1073/pnas.87.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Foss F. M., Veillette A., Sartor O., Rosen N., Bolen J. B. Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells. Oncogene Res. 1989;5(1):13–23. [PubMed] [Google Scholar]
  22. 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]
  23. Giordano T., Howard T. H., Coleman J., Sakamoto K., Howard B. H. Isolation of a population of transiently transfected quiescent and senescent cells by magnetic affinity cell sorting. Exp Cell Res. 1991 Jan;192(1):193–197. doi: 10.1016/0014-4827(91)90175-t. [DOI] [PubMed] [Google Scholar]
  24. Goldstein S., Fordis C. M., Howard B. H. Enhanced transfection efficiency and improved cell survival after electroporation of G2/M-synchronized cells and treatment with sodium butyrate. Nucleic Acids Res. 1989 May 25;17(10):3959–3971. doi: 10.1093/nar/17.10.3959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Goodrich D. W., Wang N. P., Qian Y. W., Lee E. Y., Lee W. H. The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle. Cell. 1991 Oct 18;67(2):293–302. doi: 10.1016/0092-8674(91)90181-w. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Gu W., Schneider J. W., Condorelli G., Kaushal S., Mahdavi V., Nadal-Ginard B. Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation. Cell. 1993 Feb 12;72(3):309–324. doi: 10.1016/0092-8674(93)90110-c. [DOI] [PubMed] [Google Scholar]
  28. Hamel P. A., Cohen B. L., Sorce L. M., Gallie B. L., Phillips R. A. Hyperphosphorylation of the retinoblastoma gene product is determined by domains outside the simian virus 40 large-T-antigen-binding regions. Mol Cell Biol. 1990 Dec;10(12):6586–6595. doi: 10.1128/mcb.10.12.6586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hiebert S. W., Chellappan S. P., Horowitz J. M., Nevins J. R. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992 Feb;6(2):177–185. doi: 10.1101/gad.6.2.177. [DOI] [PubMed] [Google Scholar]
  30. Hinds P. W., Mittnacht S., Dulic V., Arnold A., Reed S. I., Weinberg R. A. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell. 1992 Sep 18;70(6):993–1006. doi: 10.1016/0092-8674(92)90249-c. [DOI] [PubMed] [Google Scholar]
  31. Hu Q. J., Lees J. A., Buchkovich K. J., Harlow E. The retinoblastoma protein physically associates with the human cdc2 kinase. Mol Cell Biol. 1992 Mar;12(3):971–980. doi: 10.1128/mcb.12.3.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Isaacs W. B., Carter B. S., Ewing C. M. Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res. 1991 Sep 1;51(17):4716–4720. [PubMed] [Google Scholar]
  33. Kaelin W. G., Jr, Pallas D. C., DeCaprio J. A., Kaye F. J., Livingston D. M. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 1991 Feb 8;64(3):521–532. doi: 10.1016/0092-8674(91)90236-r. [DOI] [PubMed] [Google Scholar]
  34. Kalderon D., Smith A. E. In vitro mutagenesis of a putative DNA binding domain of SV40 large-T. Virology. 1984 Nov;139(1):109–137. doi: 10.1016/0042-6822(84)90334-9. [DOI] [PubMed] [Google Scholar]
  35. Kato J., Matsushime H., Hiebert S. W., Ewen M. E., Sherr C. J. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993 Mar;7(3):331–342. doi: 10.1101/gad.7.3.331. [DOI] [PubMed] [Google Scholar]
  36. Kosaka M., Nishina Y., Takeda M., Matsumoto K., Nishimune Y. Reversible effects of sodium butyrate on the differentiation of F9 embryonal carcinoma cells. Exp Cell Res. 1991 Jan;192(1):46–51. doi: 10.1016/0014-4827(91)90155-n. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Lin J. Y., Simmons D. T. Stable T-p53 complexes are not required for replication of simian virus 40 in culture or for enhanced phosphorylation of T antigen and p53. J Virol. 1991 Apr;65(4):2066–2072. doi: 10.1128/jvi.65.4.2066-2072.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Ludlow J. W., Glendening C. L., Livingston D. M., DeCarprio J. A. Specific enzymatic dephosphorylation of the retinoblastoma protein. Mol Cell Biol. 1993 Jan;13(1):367–372. doi: 10.1128/mcb.13.1.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Martin R. G., Setlow V. P., Edwards C. A., Vembu D. The roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells. Cell. 1979 Jul;17(3):635–643. doi: 10.1016/0092-8674(79)90271-x. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Mittnacht S., Weinberg R. A. G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell. 1991 May 3;65(3):381–393. doi: 10.1016/0092-8674(91)90456-9. [DOI] [PubMed] [Google Scholar]
  45. Mumby M. C., Walter G. Protein phosphatases and DNA tumor viruses: transformation through the back door? Cell Regul. 1991 Aug;2(8):589–598. doi: 10.1091/mbc.2.8.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. Naranjo J. R., Mellström B., Auwerx J., Mollinedo F., Sassone-Corsi P. Unusual c-fos induction upon chromaffin PC12 differentiation by sodium butyrate: loss of fos autoregulatory function. Nucleic Acids Res. 1990 Jun 25;18(12):3605–3610. doi: 10.1093/nar/18.12.3605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Partridge J. F., La Thangue N. B. A developmentally regulated and tissue-dependent transcription factor complexes with the retinoblastoma gene product. EMBO J. 1991 Dec;10(12):3819–3827. doi: 10.1002/j.1460-2075.1991.tb04951.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Reddy V. B., Thimmappaya B., Dhar R., Subramanian K. N., Zain B. S., Pan J., Ghosh P. K., Celma M. L., Weissman S. M. The genome of simian virus 40. Science. 1978 May 5;200(4341):494–502. doi: 10.1126/science.205947. [DOI] [PubMed] [Google Scholar]
  51. Ruediger R., Roeckel D., Fait J., Bergqvist A., Magnusson G., Walter G. Identification of binding sites on the regulatory A subunit of protein phosphatase 2A for the catalytic C subunit and for tumor antigens of simian virus 40 and polyomavirus. Mol Cell Biol. 1992 Nov;12(11):4872–4882. doi: 10.1128/mcb.12.11.4872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sakamoto K., Fordis C. M., Corsico C. D., Howard T. H., Howard B. H. Modulation of HeLa cell growth by transfected 7SL RNA and Alu gene sequences. J Biol Chem. 1991 Feb 15;266(5):3031–3038. [PubMed] [Google Scholar]
  53. Sakamoto K., Howard T., Ogryzko V., Xu N. Z., Corsico C. C., Jones D. H., Howard B. Relative mitogenic activities of wild-type and retinoblastoma binding-defective SV40 T antigens in serum-deprived and senescent human diploid fibroblasts. Oncogene. 1993 Jul;8(7):1887–1893. [PubMed] [Google Scholar]
  54. Scheidtmann K. H., Mumby M. C., Rundell K., Walter G. Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen. Mol Cell Biol. 1991 Apr;11(4):1996–2003. doi: 10.1128/mcb.11.4.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Scheidtmann K. H., Virshup D. M., Kelly T. J. Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity. J Virol. 1991 Apr;65(4):2098–2101. doi: 10.1128/jvi.65.4.2098-2101.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. 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]
  57. Sleigh M. J., Topp W. C., Hanich R., Sambrook J. F. Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells. Cell. 1978 May;14(1):79–88. doi: 10.1016/0092-8674(78)90303-3. [DOI] [PubMed] [Google Scholar]
  58. Sontag E., Fedorov S., Kamibayashi C., Robbins D., Cobb M., Mumby M. The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation. Cell. 1993 Dec 3;75(5):887–897. doi: 10.1016/0092-8674(93)90533-v. [DOI] [PubMed] [Google Scholar]
  59. Sugano S., Yamaguchi N., Shimojo H. Small t protein of simian virus 40 is required for dense focus formation in a rat cell line. J Virol. 1982 Mar;41(3):1073–1075. doi: 10.1128/jvi.41.3.1073-1075.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Takahashi R., Hashimoto T., Xu H. J., Hu S. X., Matsui T., Miki T., Bigo-Marshall H., Aaronson S. A., Benedict W. F. The retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5257–5261. doi: 10.1073/pnas.88.12.5257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tang S. J., Ko L. W., Lee Y. H., Wang F. F. Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation. Biochim Biophys Acta. 1990 Jan 30;1048(1):59–65. doi: 10.1016/0167-4781(90)90022-t. [DOI] [PubMed] [Google Scholar]
  62. Templeton D. J., Park S. H., Lanier L., Weinberg R. A. Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3033–3037. doi: 10.1073/pnas.88.8.3033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Thomas N. S., Burke L. C., Bybee A., Linch D. C. The phosphorylation state of the retinoblastoma (RB) protein in G0/G1 is dependent on growth status. Oncogene. 1991 Feb;6(2):317–322. [PubMed] [Google Scholar]
  64. Wang H. G., Draetta G., Moran E. E1A induces phosphorylation of the retinoblastoma protein independently of direct physical association between the E1A and retinoblastoma products. Mol Cell Biol. 1991 Aug;11(8):4253–4265. doi: 10.1128/mcb.11.8.4253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. 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]
  66. Williams R. T., Carbonaro-Hall D. A., Hall F. L. Co-purification of p34cdc2/p58cyclin A proline-directed protein kinase and the retinoblastoma tumor susceptibility gene product: interaction of an oncogenic serine/threonine protein kinase with a tumor-suppressor protein. Oncogene. 1992 Mar;7(3):423–432. [PubMed] [Google Scholar]
  67. Yang S. I., Lickteig R. L., Estes R., Rundell K., Walter G., Mumby M. C. Control of protein phosphatase 2A by simian virus 40 small-t antigen. Mol Cell Biol. 1991 Apr;11(4):1988–1995. doi: 10.1128/mcb.11.4.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Zerrahn J., Deppert W. Analysis of simian virus 40 small t antigen-induced progression of rat F111 cells minimally transformed by large T antigen. J Virol. 1993 Mar;67(3):1555–1563. doi: 10.1128/jvi.67.3.1555-1563.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. 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]
  70. de Ronde A., Sol C. J., van Strien A., ter Schegget J., van der Noordaa J. The SV40 small t antigen is essential for the morphological transformation of human fibroblasts. Virology. 1989 Jul;171(1):260–263. doi: 10.1016/0042-6822(89)90534-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES