Abstract
Regulation of cell proliferation is achieved by the tight control of the progression through the cell cycle which controls the transition of cells between quiescent and growing states. This regulation relies on the coordinated balance between inhibitory and stimulatory signals. The stimulatory factors (e.g., growth factors) and their receptors are often encoded by a class of genes called proto-oncogenes. Cells also contain several inhibitory proteins, encoded by tumor suppressor genes which act as either censors or pacers (Marx, 1994).
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References
Azizkhan, J. C., Jensen, D. E., Pierce, A. J. and Wade, M., 1993, Transcription from TATA-less promoters: dihydrofolate reductase as a model. Critical Reviews in Eukaryotic Gene Expression3: 229–254.
Azizkhan, J. C., Vaughn, J. P., Christy, R. J. and Hamlin, J. L., 1986, Nucleotide sequence and nuclease hypersensitivity of the Chinese hamster dihydrofolate reductase gene promoter region. Biochemistry25: 6228–6236.
Bandara, L. R., Buck, V. M., Zamanian, M., Johnston, L. H. and La Thangue, N. B., 1993, Functional synergy between DP-1 and E2F-I in the cell cycle-regulating transcription factor DRTF I/E2F. EMBO Journal12: 4317–4324.
Beijersbergen, R. L., Hijmans, E. M., Zhu, L. and Bernards, R., 1994, Interaction of c-myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. EMBO Journal13: 4080–4086.
Beijersbergen, R. L., Kerkhoven, R. M., Zhu, L., Carlee, L., Voorhoeve, P. M. and Bernards, R., 1994, E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes Dev. 8: 2680–2690.
Blake, M. C. and Azizkhan, J. C., 1989, Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. Mol. Cell. Biol.9: 4994–5002.
Blake, M. C., Jambou, R. C., Swick, A. G., Kahn, J. W. and Azizkhan, J. C., 1990, Transcriptional initiation is controlled by upstream GC-box interactions in a TATAA-less promoter. Mol. Cell. Biol.10: 6632–6641.
Borellini, F. and Glazer, R. I., 1993, Induction of Spl-p53 DNA-binding heterocomplexes during granulocyte/macrophage colony-stimulating factor-dependent proliferation in human erythroleukemia cell line TF-1. J. Biol. Chem.268: 7923–7928.
Buchkovich, K., Duffy, L. A. and Harlow, E., 1989, The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell 58: 1097–1105.
Chellappan, S. P., Hiebert, S., Mudryj, M., Horowitz, J. M. and Nevins, J. R., 1991, The E2F transcription factor is a cellular target for the RB protein. Cell65: 1053–1061.
Chen, L. I., Nishinaka, T., Kwan, K., Kitabayashi, I., Yokoyama, K., Fu, Y. H., Grunwald, S. and Chiu, R., 1994, The retinoblastoma gene product RB stimulates Spl-mediated transcription by liberating Spl from a negative regulator. Mol. Cell. Biol.14: 4380–4389.
Chen, P. L., Scully, P., Shew, J. Y., Wang, J. Y. and Lee, W. H., 1989, Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell58: 1193–1198.
Chittenden, T., Livingston, D. M. and Kaelin, W. G., Jr, 1991, The T/EIA-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein. Cell65: 1073–1082.
Courey, A. J., Holtzman, D. A., Jackson, S. P. and Tjian, R., 1989, Synergistic activation by the glutamine-rich domains of human transcription factor Spl. Cell59: 827–836.
Dusing, M. R. and Wiginton, D. A., 1994, Spl is essential for bath enhancer-mediated and basal activation of the TATA-less human adenosine deaminase promoter. Nucleic Acids Research22: 669–677.
Dynan, W. S. and Tjian, R., 1983, Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell32: 669–680.
Dynlacht, B. D., Brook, A., Dembski, M., Yenush, L. and Dyson, N., 1994, DNA-binding and trans-activation properties of Drosophila E2F and DP proteins. Proc. Nat. Acad. Sci. USA91: 6359–6363.
Feder, J. N., Guidos, C. J., Kusler, B., Carswell, C., Lewis, D. and Schimke, R. T., 1990, A cell cycle analysis of growth-related genes expressed during T lymphocyte maturation. J. Cell Biol.111: 2693–2701.
Gibson, T. J., Thompson, J. D., Blocker, A. and Kouzarides, T., 1994, Evidence of a protein domain superfamily shared by the cyclins, TFIIB and pRB/p107. Nuc. Acids Res.22: 946–952.
Gill, G., Pascal, E., Tseng, Z. H. and Tjian, R., 1994, A glutamine-rich hydrophobic patch in transcription factor Spl contacts the dTAFII110 component of the Drosophila TFIID complex and mediates transcriptional activation. Proc. Nat. Acad. Sci. USA91: 192–196.
Gill, R. M., Hamel, R A., Jiang, Z., Zacksenhaus, E., Gallic, B. L. and Phillips, R. A., 1994, Characterization of the human RBI promoter and of elements involved in transcriptional regulation. Cell Growth & Differentiation 5: 467–474.
Gottlieb, T. M. and Jackson, S. R, 1993, The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell 72: 131–142.
Hagemeier, C., Bannister, A. J., Cook, A. and Kouzarides, T., 1993, The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proc. Nat. Acad. Sci. USA90: 1580–1584.
Hakala, M. T. and Taylor, E., 1959, The ability of purine and thymidine derivatives and of glycine to support the growth of mammalian cells in culture. J. Biol. Chem.234: 126–128.
Haug, T., Skorpen, F., Lund, H. and Krokan, H. E., 1994, Structure of the gene for human uracil-DNA glycosylase and analysis of the promoter function. FEBS Letters353: 180–4.
Helin, K., Lees, J. A., Vidal, M., Dyson, N., Harlow, E. and Fattaey, A., 1992, A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell70: 337–350.
Henglein, B., Chenivesse, X., Wang, J., Eick, D. and Brechot, C., 1994, Structure and cell cycle-regulated transcription of the human cyclin A gene. Proc. Nat. Acad. Sci. USA91: 5490–5494.
Hiebert, S. W., 1993, Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression. Mol. Cell. Biol.13: 3384–3391.
Hiebert, S. W., Chellappan, S. R, Horowitz, J. M. and Nevins. J. R., 1992, The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dey. 6: 177–185.
Huang, S., Shin, E., Sheppard, K. A., Chokroverty, L., Shan, B., Qian, Y. W., Lee, E. Y. and Yee, A. S., 1992, The retinoblastoma protein region required for interaction with the E2F transcription factor includes the T/E I A binding and carboxy-terminal sequences. DNA Cell Biol. 11: 539–548.
Hunter, T. and Pines, J., 1991, Cyclins and Cancer. Cell 68: 1071–1074.
Ivey-Hoyle, M., Conroy, R., Huber, H. E., Goodhart, P. J., Oliff, A. and Heimbrook, D. C., 1993, Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. Mol. Cell. Biol.13: 7802–7812.
Jackson, S., Gottlieb, T. and Hartley, K., 1993, Phosphorylation of transcription factor Spl by the DNA-dependent protein kinase. Adv Second Messenger Phosphoprotein Res. 28: 279–286.
Jackson, S. P., 1992, Regulating transcription factor activity by phosphorylation. Tr Cell Biol. 2: 104–108.
Jackson, S. P., MacDonald, J. J., Lees-Miller, S. and Tjian, R., 1990, GC box binding induces phosphorylation of Spl by a DNA-dependent protein kinase. Cell 63: 155–165.
Johnson, D. G., Cress, W. D., Jakoi, L. and Nevins, J. R., 1994, Oncogenic capacity of the E2F1 gene. Proc. Nat. Acad. Sci., USA91: 12823–12827.
Johnson, J. L. and McLachlan, A., 1994, Novel clustering of Spl transcription factor binding sites at the transcription initiation site of the human muscle phosphofructokinase P1 promoter. Nuc. Acids Res.22: 5085–5092.
Jolliff, K., Li, Y. and Johnson, L. F., 1991, Multiple protein-DNA interactions in the TATAA-less mouse thymidylate synthase promoter. Nuc. Acids Res19: 2267–2274.
Kadonaga, J. T., Camer, K. R., Masiarz, F. R. and Tjian, R., 1987, Isolation of cDNA encoding transcription factor Sp I and functional analysis of the DNA binding domain. Cell 51: 1079–1090.
Kaelin, W. G., Krek, W., Sellers, W. R., DeCaprio, J. A., Ajchanbaum, F., Fuchs, C. S., Chittenden, T., Li, Y., Farnham, P. J., Blanar, M. A., Livingston, D. M. and Flemington, E. K., 1992, Expression cloning of a cDNA encoding a retinoblastoma binding protein with E2F-like properties. Cell 70: 351–364.
Kim, S. J., Onwuta, U. S., Lee, Y. I., Li, R., Botchan, M. R. and Robbins, R. D., 1992, The retinoblastoma gene product regulates Spl-mediated transcription. Mol. Cell. Biol.12: 2455–2463.
Kovesdi, I., Reichel, R. and Nevins, J. R., 1986, Identification of a cellular transcription factor involved in EIA trans-activation. Cell 45: 219–228.
Lee, H. H., Chiang, W. H., Chiang, S. H., Liu, Y. C., Hwang, J. and Ng, S. Y., 1995, Regulation of cyclin Dl, DNA topoisomerase I, and proliferating cell nuclear antigen promoters during the cell cycle. Gene Expression 4: 95–109.
Lee, W. H., Shew, J. Y., Hong, F. D., Sery, T. W., Donoso, L. A., Young, L. J., Bookstein, R. and Lee, E. Y., 1987, The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature (London) 329: 624–645.
Lees, J. A., Saito, M., Vidal, M., Valentine, M., Look, T., Harlow, E., Dyson, N. and Helin, K., 1993, The retinoblastoma protein binds to a family of E2F transcription factors. Molecular & Cellular Biology 13: 7813–25.
Li, Y., Slansky, J. E., Myers, D. J., Drinkwater, N. R., Kaelin, W. G. and Farnham, R. J., 1994, Cloning, chromosomal location, and characterization of mouse E2F1. Mol. Cell. Biol. 14: 1861–1869.
Liao, W. C., Ash, J. and Johnson, L. F., 1994, Bidirectional promoter of the mouse thymidylate synthase gene. Nuc. Acids Res. 22: 4044–4049.
Lu, J., Lee, W., Jiang, C. and Keller, E. B., 1994, Start site selection by Spl in the TATA-less human Ha-ras promoter. J. Biol. Chem. 269: 5391–402.
Ludlow, J. W., DeCaprio, J. A., Huang, G.-M., Lee, W.-H., Paucha, E. and Livingston, D. M., 1989, SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma suxceptibility gene product family. Cell 56: 57–65.
Marx, J., 1994, Science264: 344–345.
Means, A. L., Slansky, J., E., McMahon, S. L., Knuth, M. W. and Farnham, P. J., 1992, The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. Mol. Cell. Biol. 12: 1054–1063.
Motokura, T. and Arnold, A., 1993, PRAD1/cyclin D1 proto-oncogene: Genomic organization, 5’ DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes, Chromosomes, and Cancer 7: 89–95.
Mudryj, M., Devoto, S. H., Hiebert, S. W., Hunter, T., Pines, J. and Nevins, J. R., 1991, Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell 65: 1243–53.
Murata, Y., Kim, H. G., Rogers, K. T., Udvadia, A. J. and Horowitz, J. M., 1994, Negative regulation of Sp I trans-activation is correlated with the binding of cellular proteins to the amino terminus of the Spl trans-activation domain. J. Biol. Chem. 269: 20674–20681.
Neuman, E., Flemington, E. K., Sellers, W. R. and Kaelin, W. G., Jr., 1994, Transcription of the E2F-I gene is rendered cell cycle dependent by E2F DNA binding within its own promoter. Mol. Cell. Biol. 14: 6607–6615.
Neumann, J. R., Morency, C. A. and Russian, K. O.. 1987, A rapid fluor diffusion assay for detection of chloramphenicol acetyl transferase activity. Biotechniques 5: 444–448.
Nevins, J. R., 1992, E2F: A link between the Rb tumor suppressor protein and viral oncoproteins. Science 258: 424–429.
Ogris, E., Rotheneder, H., Mudrak, I., Pichler, A. and Wintersberger, E., 1993, A binding site for transcription factor E2F is a target for trans activation of murine thymidine kinase by polyomavirus large T antigen and plays an important role in growth regulation of the gene. J. Virol. 67: 1765–1771.
Ohtani, K., Nevins, J. R., Dou, Q. P., Zhao, S., Levin, A. H., Wang, J., Helin, K. and Pardee, A. B., 1994, Functional properties of a Drosophila homolog of the E2FI gene GUS-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter. Mol. Cell. Biol. 14: 1603–1612.
Ouellette, M. M., Chen, J., Wright, W. E. and Shay, J. W., 1992, Complexes containing the retinoblastoma gene product recognize different DNA motifs related to the E2F binding site. Oncogene 7: 1075–1081.
Pardee, A. B., 1989, GI events and regulation of cell proliferation. Science 246: 603–608.
Pearson, B. E., Nasheuer, H.-P. and Wang, T. S.-F., 1991, Human DNA polymerase a hene: Sequences controlling expression in cycling and serum-stimulated cells. Mol. Cell. Biol. 11: 2081–2095.
Qin, X. Q., Livingston, D. M., Kaelin, W. G., Jr. and Adams, P. D., 1994, Deregulated transcription factor E2F-I expression leads to S-phase entry and p53-mediated apoptosis. Proc. Nat. Acad. Sci. U.S.A. 91: 10918–10922.
Saffer, J. D., Jackson, S. P. and Annarella, M. B., 1991, Developmental expression of Spl in the mouse. Mol. Cell. Biol. 11: 2189–2199.
Santiago, C., Collins, M. and Johnson, L. F., 1984, In vitro and in vivo analysis of the control of dihydrofolate reductase gene transcription in serum-stimulated mouse fibroblasts. J. Cell. Physiol. 118: 79–86.
Seto, E., Lewis, B. and Shenk, T., 1993, Interaction between transcription factors Spl and YY1. Nature 365: 462–464.
Seto, E., Shi, Y. and Shenk, T., 1991, YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature 354: 241–245.
Shan, B., Chang, C. Y., Jones, D. and Lee, W. H., 1994, The transcription factor E2F-1 mediates the autoregulation of RB gene expression. Mol. Cell. Biol. 14: 299–309.
Shan, B. and Lee, W. H., 1994, Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol. Cell. Biol. 14: 8166–8173.
Shao, Z. and Robbins, P. D., 1995, Differential regulation of E2F and Spl-mediated transcription by GI cyclins. Oncogene 10: 221–228.
Singh, P., Wong, S. H. and Hong, W., 1994, Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation. EMBO Journal 13: 3329–3338.
Swick, A. G., Blake, M. C., Kahn, J. W. and Azizkhan, J. C., 1989, Functional analysis of GC element binding and transcription in the hamster dihydrofolate reductase gene promoter. Nucleic Acids Res. 17: 9291–9304.
Udvadia, A. J., Rogers, K. T., Higgins, P. D., Murata, Y., Martin, K. H., Humphrey, P. A. and Horowitz, J. M., 1993, Sp-1 binds promoter elements regulated by the RB protein and Sp-l-mediated transcription is stimulated by RB coexpression. Proc. Nat. Acad. Sci. USA 90: 3265–3269.
Wade, M., Blake, M. C., Jambou, R. C., Helin, K., Harlow, E. and Azizkhan, J. C., 1995, An inverted repeat motif stabilizes binding of E2F and enhances transcription of the dihydrofolate reductase gene. J. Biol. Chem. 270: 9783–9791.
Weintraub, S. J. and Dean, D. C., 1992, Interaction of a common factor with ATF, Spl, or TATAA promoter elements is required for these sequences to mediate transactivation by the adenoviral oncogene Ela. Mol. Cell. Biol. 12: 512–517.
Xu, G. F., Livingston, D. M. and Krek, W., 1995, Multiple members of the E2F transcription factor family are the products of oncogenes. Proc. Nat. Acad. Sci., USA 92: 1357–1361.
Yamamoto, M., Yoshida, M., Ono, K., Fujita, T., Ohtani-Fujita, N., Sakai, T. and Nikaido, T., 1994, Effect of tumor suppressors on cell cycle regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression. Experimental Cell Research 210: 94–101.
Zacksenhaus, E., Bremner, R., Phillips, R. A. and Gallie, B. L., 1993, A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity. Mol. Cell. Biol. 13: 4588–4599.
Zhang, D. E., Hetherington, C. J., Tan, S., Dziennis, S. E., Gonzalez, D. A., Chen, H. M. and Tenen, D. G., 1994, Spi is a critical factor in monocyte specific expression of human CD14. J. Biol. Chem. 268: 11425–11434.
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Azizkhan, J.C., Lin, S.Y., Jensen, D., Kostic, D., Black, A.R. (1996). Retinoblastoma Protein, Gene Expression, and Cell Cycle Control. In: Mihich, E., Housman, D. (eds) Cancer Genes. Pezcoller Foundation Symposia, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5895-8_10
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