Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1996 Nov;70(11):7867–7877. doi: 10.1128/jvi.70.11.7867-7877.1996

The human cytomegalovirus IE1-72 protein interacts with the cellular p107 protein and relieves p107-mediated transcriptional repression of an E2F-responsive promoter.

E E Poma 1, T F Kowalik 1, L Zhu 1, J H Sinclair 1, E S Huang 1
PMCID: PMC190858  PMID: 8892909

Abstract

The Rb-related p107 protein has been implicated as an important control element in proper cell cycle progression. The p107 protein is thought to restrict cellular proliferation in part through its interaction with the E2F family of transcription factors and is, therefore, a specific target for regulation by several DNA viruses. Here, we demonstrate that p107 protein levels are induced in a biphasic manner in human fibroblasts during productive infection by the human cytomegalovirus (HCMV). Expression patterns of p107 protein levels during HCMV infection of human embryonic lung cells (HELs) demonstrate a sustained induction from early to late times of infection. We also demonstrate that the HCMV immediate-early protein IE1-72 complexes in vivo with the p107 protein and that this interaction can be reconstituted in an in vitro system by using reticulocyte-translated protein. Our data demonstrate that the interaction between p107 and the IE1-72 protein occurs at times of infection that temporally match the second tier of p107 protein induction and the phosphorylation pattern of the IE1-72 protein. Furthermore, we show here that the ability of p107 to transcriptionally repress E2F-responsive promoters can be overcome by expression of the IE1-72 protein. This effect appears to be specific, since the IE1-72 protein is not capable of relieving Rb-mediated repression of an E2F-responsive promoter. Finally, our data demonstrate that HCMV infection can induce cellular proliferation in quiescent cells and that IE1-72 expression alone can, to a degree, drive a similar progression through the cell cycle. These data suggest that IE1-72-mediated transactivation of E2F-responsive promoters through alleviation of p107 transcriptional repression may play a key role in the cell cycle progression stimulated by HCMV infection.

Full Text

The Full Text of this article is available as a PDF (404.1 KB).

Selected References

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

  1. Arlt H., Lang D., Gebert S., Stamminger T. Identification of binding sites for the 86-kilodalton IE2 protein of human cytomegalovirus within an IE2-responsive viral early promoter. J Virol. 1994 Jul;68(7):4117–4125. doi: 10.1128/jvi.68.7.4117-4125.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baracchini E., Glezer E., Fish K., Stenberg R. M., Nelson J. A., Ghazal P. An isoform variant of the cytomegalovirus immediate-early auto repressor functions as a transcriptional activator. Virology. 1992 Jun;188(2):518–529. doi: 10.1016/0042-6822(92)90506-k. [DOI] [PubMed] [Google Scholar]
  3. Beijersbergen R. L., Carlée L., Kerkhoven R. M., Bernards R. Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Genes Dev. 1995 Jun 1;9(11):1340–1353. doi: 10.1101/gad.9.11.1340. [DOI] [PubMed] [Google Scholar]
  4. Biegalke B. J., Geballe A. P. Sequence requirements for activation of the HIV-1 LTR by human cytomegalovirus. Virology. 1991 Jul;183(1):381–385. doi: 10.1016/0042-6822(91)90151-z. [DOI] [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. Caswell R., Hagemeier C., Chiou C. J., Hayward G., Kouzarides T., Sinclair J. The human cytomegalovirus 86K immediate early (IE) 2 protein requires the basic region of the TATA-box binding protein (TBP) for binding, and interacts with TBP and transcription factor TFIIB via regions of IE2 required for transcriptional regulation. J Gen Virol. 1993 Dec;74(Pt 12):2691–2698. doi: 10.1099/0022-1317-74-12-2691. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Cherrington J. M., Khoury E. L., Mocarski E. S. Human cytomegalovirus ie2 negatively regulates alpha gene expression via a short target sequence near the transcription start site. J Virol. 1991 Feb;65(2):887–896. doi: 10.1128/jvi.65.2.887-896.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cherrington J. M., Mocarski E. S. Human cytomegalovirus ie1 transactivates the alpha promoter-enhancer via an 18-base-pair repeat element. J Virol. 1989 Mar;63(3):1435–1440. doi: 10.1128/jvi.63.3.1435-1440.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chiou C. J., Zong J., Waheed I., Hayward G. S. Identification and mapping of dimerization and DNA-binding domains in the C terminus of the IE2 regulatory protein of human cytomegalovirus. J Virol. 1993 Oct;67(10):6201–6214. doi: 10.1128/jvi.67.10.6201-6214.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Choi K. S., Kim S. J., Kim S. The retinoblastoma gene product negatively regulates transcriptional activation mediated by the human cytomegalovirus IE2 protein. Virology. 1995 Apr 20;208(2):450–456. doi: 10.1006/viro.1995.1175. [DOI] [PubMed] [Google Scholar]
  12. Cobrinik D., Whyte P., Peeper D. S., Jacks T., Weinberg R. A. Cell cycle-specific association of E2F with the p130 E1A-binding protein. Genes Dev. 1993 Dec;7(12A):2392–2404. doi: 10.1101/gad.7.12a.2392. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Davis M. G., Huang E. S. Transfer and expression of plasmids containing human cytomegalovirus immediate-early gene 1 promoter-enhancer sequences in eukaryotic and prokaryotic cells. Biotechnol Appl Biochem. 1988 Feb;10(1):6–12. [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Depto A. S., Stenberg R. M. Functional analysis of the true late human cytomegalovirus pp28 upstream promoter: cis-acting elements and viral trans-acting proteins necessary for promoter activation. J Virol. 1992 May;66(5):3241–3246. doi: 10.1128/jvi.66.5.3241-3246.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Depto A. S., Stenberg R. M. Regulated expression of the human cytomegalovirus pp65 gene: octamer sequence in the promoter is required for activation by viral gene products. J Virol. 1989 Mar;63(3):1232–1238. doi: 10.1128/jvi.63.3.1232-1238.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Dyson N., Guida P., Münger K., Harlow E. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J Virol. 1992 Dec;66(12):6893–6902. doi: 10.1128/jvi.66.12.6893-6902.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dyson N. pRB, p107 and the regulation of the E2F transcription factor. J Cell Sci Suppl. 1994;18:81–87. doi: 10.1242/jcs.1994.supplement_18.12. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Furnari B. A., Poma E., Kowalik T. F., Huong S. M., Huang E. S. Human cytomegalovirus immediate-early gene 2 protein interacts with itself and with several novel cellular proteins. J Virol. 1993 Aug;67(8):4981–4991. doi: 10.1128/jvi.67.8.4981-4991.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ghazal P., Young J., Giulietti E., DeMattei C., Garcia J., Gaynor R., Stenberg R. M., Nelson J. A. A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-early proteins. J Virol. 1991 Dec;65(12):6735–6742. doi: 10.1128/jvi.65.12.6735-6742.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Hagemeier C., Caswell R., Hayhurst G., Sinclair J., Kouzarides T. Functional interaction between the HCMV IE2 transactivator and the retinoblastoma protein. EMBO J. 1994 Jun 15;13(12):2897–2903. doi: 10.1002/j.1460-2075.1994.tb06584.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hagemeier C., Walker S. M., Sissons P. J., Sinclair J. H. The 72K IE1 and 80K IE2 proteins of human cytomegalovirus independently trans-activate the c-fos, c-myc and hsp70 promoters via basal promoter elements. J Gen Virol. 1992 Sep;73(Pt 9):2385–2393. doi: 10.1099/0022-1317-73-9-2385. [DOI] [PubMed] [Google Scholar]
  28. Hagemeier C., Walker S., Caswell R., Kouzarides T., Sinclair J. The human cytomegalovirus 80-kilodalton but not the 72-kilodalton immediate-early protein transactivates heterologous promoters in a TATA box-dependent mechanism and interacts directly with TFIID. J Virol. 1992 Jul;66(7):4452–4456. doi: 10.1128/jvi.66.7.4452-4456.1992. [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. Hayhurst G. P., Bryant L. A., Caswell R. C., Walker S. M., Sinclair J. H. CCAAT box-dependent activation of the TATA-less human DNA polymerase alpha promoter by the human cytomegalovirus 72-kilodalton major immediate-early protein. J Virol. 1995 Jan;69(1):182–188. doi: 10.1128/jvi.69.1.182-188.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Herber B., Truss M., Beato M., Müller R. Inducible regulatory elements in the human cyclin D1 promoter. Oncogene. 1994 Apr;9(4):1295–1304. [PubMed] [Google Scholar]
  32. Hermiston T. W., Malone C. L., Stinski M. F. Human cytomegalovirus immediate-early two protein region involved in negative regulation of the major immediate-early promoter. J Virol. 1990 Jul;64(7):3532–3536. doi: 10.1128/jvi.64.7.3532-3536.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hermiston T. W., Malone C. L., Witte P. R., Stinski M. F. Identification and characterization of the human cytomegalovirus immediate-early region 2 gene that stimulates gene expression from an inducible promoter. J Virol. 1987 Oct;61(10):3214–3221. doi: 10.1128/jvi.61.10.3214-3221.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Herzinger T., Wolf D. A., Eick D., Kind P. The pRb-related protein p130 is a possible effector of transforming growth factor beta 1 induced cell cycle arrest in keratinocytes. Oncogene. 1995 Jun 1;10(11):2079–2084. [PubMed] [Google Scholar]
  35. Hiebert S. W., Packham G., Strom D. K., Haffner R., Oren M., Zambetti G., Cleveland J. L. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol Cell Biol. 1995 Dec;15(12):6864–6874. doi: 10.1128/mcb.15.12.6864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Hu Q. J., Dyson N., Harlow E. The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations. EMBO J. 1990 Apr;9(4):1147–1155. doi: 10.1002/j.1460-2075.1990.tb08221.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Huang E. S., Chen S. T., Pagano J. S. Human cytomegalovirus. I. Purification and characterization of viral DNA. J Virol. 1973 Dec;12(6):1473–1481. doi: 10.1128/jvi.12.6.1473-1481.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Huang S., Wang N. P., Tseng B. Y., Lee W. H., Lee E. H. Two distinct and frequently mutated regions of retinoblastoma protein are required for binding to SV40 T antigen. EMBO J. 1990 Jun;9(6):1815–1822. doi: 10.1002/j.1460-2075.1990.tb08306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Jault F. M., Jault J. M., Ruchti F., Fortunato E. A., Clark C., Corbeil J., Richman D. D., Spector D. H. Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. J Virol. 1995 Nov;69(11):6697–6704. doi: 10.1128/jvi.69.11.6697-6704.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Jault F. M., Jault J. M., Ruchti F., Fortunato E. A., Clark C., Corbeil J., Richman D. D., Spector D. H. Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. J Virol. 1995 Nov;69(11):6697–6704. doi: 10.1128/jvi.69.11.6697-6704.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Jupp R., Hoffmann S., Depto A., Stenberg R. M., Ghazal P., Nelson J. A. Direct interaction of the human cytomegalovirus IE86 protein with the cis repression signal does not preclude TBP from binding to the TATA box. J Virol. 1993 Sep;67(9):5595–5604. doi: 10.1128/jvi.67.9.5595-5604.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Jupp R., Hoffmann S., Stenberg R. M., Nelson J. A., Ghazal P. Human cytomegalovirus IE86 protein interacts with promoter-bound TATA-binding protein via a specific region distinct from the autorepression domain. J Virol. 1993 Dec;67(12):7539–7546. doi: 10.1128/jvi.67.12.7539-7546.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kaelin W. G., Jr, Ewen M. E., Livingston D. M. Definition of the minimal simian virus 40 large T antigen- and adenovirus E1A-binding domain in the retinoblastoma gene product. Mol Cell Biol. 1990 Jul;10(7):3761–3769. doi: 10.1128/mcb.10.7.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. Klucher K. M., Rabert D. K., Spector D. H. Sequences in the human cytomegalovirus 2.7-kilobase RNA promoter which mediate its regulation as an early gene. J Virol. 1989 Dec;63(12):5334–5343. doi: 10.1128/jvi.63.12.5334-5343.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Klucher K. M., Sommer M., Kadonaga J. T., Spector D. H. In vivo and in vitro analysis of transcriptional activation mediated by the human cytomegalovirus major immediate-early proteins. Mol Cell Biol. 1993 Feb;13(2):1238–1250. doi: 10.1128/mcb.13.2.1238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Klucher K. M., Spector D. H. The human cytomegalovirus 2.7-kilobase RNA promoter contains a functional binding site for the adenovirus major late transcription factor. J Virol. 1990 Sep;64(9):4189–4198. doi: 10.1128/jvi.64.9.4189-4198.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. 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]
  51. Lang D., Stamminger T. The 86-kilodalton IE-2 protein of human cytomegalovirus is a sequence-specific DNA-binding protein that interacts directly with the negative autoregulatory response element located near the cap site of the IE-1/2 enhancer-promoter. J Virol. 1993 Jan;67(1):323–331. doi: 10.1128/jvi.67.1.323-331.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Liu B., Hermiston T. W., Stinski M. F. A cis-acting element in the major immediate-early (IE) promoter of human cytomegalovirus is required for negative regulation by IE2. J Virol. 1991 Feb;65(2):897–903. doi: 10.1128/jvi.65.2.897-903.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Loeken M. R., Brady J. The adenovirus EIIA enhancer. Analysis of regulatory sequences and changes in binding activity of ATF and EIIF following adenovirus infection. J Biol Chem. 1989 Apr 15;264(11):6572–6579. [PubMed] [Google Scholar]
  54. Lukac D. M., Manuppello J. R., Alwine J. C. Transcriptional activation by the human cytomegalovirus immediate-early proteins: requirements for simple promoter structures and interactions with multiple components of the transcription complex. J Virol. 1994 Aug;68(8):5184–5193. doi: 10.1128/jvi.68.8.5184-5193.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Macias M. P., Stinski M. F. An in vitro system for human cytomegalovirus immediate early 2 protein (IE2)-mediated site-dependent repression of transcription and direct binding of IE2 to the major immediate early promoter. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):707–711. doi: 10.1073/pnas.90.2.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Margolis M. J., Pajovic S., Wong E. L., Wade M., Jupp R., Nelson J. A., Azizkhan J. C. Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product with E2F1 coincides with E2F-dependent activation of dihydrofolate reductase transcription. J Virol. 1995 Dec;69(12):7759–7767. doi: 10.1128/jvi.69.12.7759-7767.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Monick M. M., Geist L. J., Stinski M. F., Hunninghake G. W. The immediate early genes of human cytomegalovirus upregulate expression of the cellular genes myc and fos. Am J Respir Cell Mol Biol. 1992 Sep;7(3):251–256. doi: 10.1165/ajrcmb/7.3.251. [DOI] [PubMed] [Google Scholar]
  58. 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]
  59. 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]
  60. 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]
  61. Philipp A., Schneider A., Väsrik I., Finke K., Xiong Y., Beach D., Alitalo K., Eilers M. Repression of cyclin D1: a novel function of MYC. Mol Cell Biol. 1994 Jun;14(6):4032–4043. doi: 10.1128/mcb.14.6.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Pizzorno M. C., Hayward G. S. The IE2 gene products of human cytomegalovirus specifically down-regulate expression from the major immediate-early promoter through a target sequence located near the cap site. J Virol. 1990 Dec;64(12):6154–6165. doi: 10.1128/jvi.64.12.6154-6165.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Pizzorno M. C., Mullen M. A., Chang Y. N., Hayward G. S. The functionally active IE2 immediate-early regulatory protein of human cytomegalovirus is an 80-kilodalton polypeptide that contains two distinct activator domains and a duplicated nuclear localization signal. J Virol. 1991 Jul;65(7):3839–3852. doi: 10.1128/jvi.65.7.3839-3852.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Pizzorno M. C., O'Hare P., Sha L., LaFemina R. L., Hayward G. S. trans-activation and autoregulation of gene expression by the immediate-early region 2 gene products of human cytomegalovirus. J Virol. 1988 Apr;62(4):1167–1179. doi: 10.1128/jvi.62.4.1167-1179.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Sambucetti L. C., Cherrington J. M., Wilkinson G. W., Mocarski E. S. NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J. 1989 Dec 20;8(13):4251–4258. doi: 10.1002/j.1460-2075.1989.tb08610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Schwartz R., Sommer M. H., Scully A., Spector D. H. Site-specific binding of the human cytomegalovirus IE2 86-kilodalton protein to an early gene promoter. J Virol. 1994 Sep;68(9):5613–5622. doi: 10.1128/jvi.68.9.5613-5622.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Schwarz J. K., Devoto S. H., Smith E. J., Chellappan S. P., Jakoi L., Nevins J. R. Interactions of the p107 and Rb proteins with E2F during the cell proliferation response. EMBO J. 1993 Mar;12(3):1013–1020. doi: 10.1002/j.1460-2075.1993.tb05742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Shan B., Lee W. H. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol Cell Biol. 1994 Dec;14(12):8166–8173. doi: 10.1128/mcb.14.12.8166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sommer M. H., Scully A. L., Spector D. H. Transactivation by the human cytomegalovirus IE2 86-kilodalton protein requires a domain that binds to both the TATA box-binding protein and the retinoblastoma protein. J Virol. 1994 Oct;68(10):6223–6231. doi: 10.1128/jvi.68.10.6223-6231.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Spector D. J., Tevethia M. J. Identification of a human cytomegalovirus virus DNA segment that complements an adenovirus 5 immediate early mutant. Virology. 1986 Jun;151(2):329–338. doi: 10.1016/0042-6822(86)90053-x. [DOI] [PubMed] [Google Scholar]
  71. Speir E., Modali R., Huang E. S., Leon M. B., Shawl F., Finkel T., Epstein S. E. Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science. 1994 Jul 15;265(5170):391–394. doi: 10.1126/science.8023160. [DOI] [PubMed] [Google Scholar]
  72. Stenberg R. M., Fortney J., Barlow S. W., Magrane B. P., Nelson J. A., Ghazal P. Promoter-specific trans activation and repression by human cytomegalovirus immediate-early proteins involves common and unique protein domains. J Virol. 1990 Apr;64(4):1556–1565. doi: 10.1128/jvi.64.4.1556-1565.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Suzuki-Takahashi I., Kitagawa M., Saijo M., Higashi H., Ogino H., Matsumoto H., Taya Y., Nishimura S., Okuyama A. The interactions of E2F with pRB and with p107 are regulated via the phosphorylation of pRB and p107 by a cyclin-dependent kinase. Oncogene. 1995 May 4;10(9):1691–1698. [PubMed] [Google Scholar]
  74. Tevethia M. J., Spector D. J., Leisure K. M., Stinski M. F. Participation of two human cytomegalovirus immediate early gene regions in transcriptional activation of adenovirus promoters. Virology. 1987 Dec;161(2):276–285. doi: 10.1016/0042-6822(87)90119-x. [DOI] [PubMed] [Google Scholar]
  75. Thalmeier K., Synovzik H., Mertz R., Winnacker E. L., Lipp M. Nuclear factor E2F mediates basic transcription and trans-activation by E1a of the human MYC promoter. Genes Dev. 1989 Apr;3(4):527–536. doi: 10.1101/gad.3.4.527. [DOI] [PubMed] [Google Scholar]
  76. Wade M., Kowalik T. F., Mudryj M., Huang E. S., Azizkhan J. C. E2F mediates dihydrofolate reductase promoter activation and multiprotein complex formation in human cytomegalovirus infection. Mol Cell Biol. 1992 Oct;12(10):4364–4374. doi: 10.1128/mcb.12.10.4364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Walker S., Hagemeier C., Sissons J. G., Sinclair J. H. A 10-base-pair element of the human immunodeficiency virus type 1 long terminal repeat (LTR) is an absolute requirement for transactivation by the human cytomegalovirus 72-kilodalton IE1 protein but can be compensated for by other LTR regions in transactivation by the 80-kilodalton IE2 protein. J Virol. 1992 Mar;66(3):1543–1550. doi: 10.1128/jvi.66.3.1543-1550.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Weinberg R. A. The retinoblastoma gene and gene product. Cancer Surv. 1992;12:43–57. [PubMed] [Google Scholar]
  79. Weintraub S. J., Chow K. N., Luo R. X., Zhang S. H., He S., Dean D. C. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature. 1995 Jun 29;375(6534):812–815. doi: 10.1038/375812a0. [DOI] [PubMed] [Google Scholar]
  80. Weintraub S. J., Prater C. A., Dean D. C. Retinoblastoma protein switches the E2F site from positive to negative element. Nature. 1992 Jul 16;358(6383):259–261. doi: 10.1038/358259a0. [DOI] [PubMed] [Google Scholar]
  81. 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]
  82. 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]
  83. Wolf D. A., Hermeking H., Albert T., Herzinger T., Kind P., Eick D. A complex between E2F and the pRb-related protein p130 is specifically targeted by the simian virus 40 large T antigen during cell transformation. Oncogene. 1995 Jun 1;10(11):2067–2078. [PubMed] [Google Scholar]
  84. Wright D. A., Staprans S. I., Spector D. H. Four phosphoproteins with common amino termini are encoded by human cytomegalovirus AD169. J Virol. 1988 Jan;62(1):331–340. doi: 10.1128/jvi.62.1.331-340.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Yamamoto M., Yoshida M., Ono K., Fujita T., Ohtani-Fujita N., Sakai T., Nikaido T. Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression. Exp Cell Res. 1994 Jan;210(1):94–101. doi: 10.1006/excr.1994.1014. [DOI] [PubMed] [Google Scholar]
  86. 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]
  87. Yurochko A. D., Kowalik T. F., Huong S. M., Huang E. S. Human cytomegalovirus upregulates NF-kappa B activity by transactivating the NF-kappa B p105/p50 and p65 promoters. J Virol. 1995 Sep;69(9):5391–5400. doi: 10.1128/jvi.69.9.5391-5400.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Zhu H., Shen Y., Shenk T. Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J Virol. 1995 Dec;69(12):7960–7970. doi: 10.1128/jvi.69.12.7960-7970.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Zhu L., Enders G., Lees J. A., Beijersbergen R. L., Bernards R., Harlow E. The pRB-related protein p107 contains two growth suppression domains: independent interactions with E2F and cyclin/cdk complexes. EMBO J. 1995 May 1;14(9):1904–1913. doi: 10.1002/j.1460-2075.1995.tb07182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Zhu L., Zhu L., Xie E., Chang L. S. Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. Mol Cell Biol. 1995 Jul;15(7):3552–3562. doi: 10.1128/mcb.15.7.3552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. 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]

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

RESOURCES