Abstract
Several observations suggest that the c-myc proto-oncogene is a key regulator of cell growth and differentiation. First, expression of c-myc RNA and protein is tightly regulated by mitogens and are suppressed by growth inhibitory agents (Luscher and Eisenman, 1991). Second, removal of c-myc protein appears required for withdrawal from the cell cycle since enforced c-myc expression promotes cell cycle progression (Askew et al., 1991; Eilers et al., 1991; Evan et al., 1992) and inhibits terminal differentiation (Prochownik and kukowska, 1986; Coppolla and Cole, 1986). Finally, inhibiton of c-myc expression by antisense oligonucleotides or RNA prevents entry of cells into S phase and accelerates differentiation (Heikkela et al, 1987; Prowchownik et al., 1988). The precise function that c-myc provides to promote cell cycle progression is unknown. Myc family proteins have domains characteristic of known transcription factors, including a basic-helix-loop-helix-(B-HLH) motif and a leucine zipper (LZ) domain, and have therefore been proposed to function as transcription factors (Luscher and Eisenman, 1991). Furthermore, it has recently been demonstrated that c-myc functions as a sequence-specific DNA binding protein (Blackwell et al., 1990; Prendergast and Ziff, 1991; Halazonetis and kandil, 1991) and through dimerization with a novel B-HLH-LZ partner, max, myc binds with high affinity to the “E-box” motif CACGTG (Blackwood and Eisenman, 1991). In addition, regions of the amino terminus of c-myc have been shown to function as transactivation domains when fused to the DNA binding domain of the transcription factor GAL4 (kato et al., 1990).
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References
Askew, D. S., Ashmun, R. A., Simmons, B. C. & Cleveland, J. L. (1991). Constitutive c-myc expression in an IL-3 dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6, 1915–1922.
Bengal, E., Ransone, L., Scharfmann, R., Dwarki, V., Tapscott, S.J., Weintraub, H. & Verma, I.M. (1992). Functional antagonism between c-jun and MyoD proteins: a direct physical association. Cell 68, 507–51
Blackwell, T. K., Kretzner, L., Blackwood, E. M., Eisenman, R. N. & Weintra B, H. (1990). Sequencespecific DNA binding by the c-myc protein. Science 250, 1149–1151.
Blackwood, E. M., and Eisenman, R. N. (1991). Max: A helix-loop-helix zipper protein that forms a sequncespecific DNA-binding complex with myc. Science 251, 1211–1217.
Blanar, M.A., & Rutter, W.J. (1992). Interaction cloning: Identification of a helix-loop-helix zipper protein that interacts with c-fos. Science 256, 1014–1018.
Bowlin T.L., Mcknown, B. & Sunkara, P. (1986). Ornithine decarboxylase induction and polyamine biosynthesis are required for growth of interleukin-2 and interleukin-3 dependent cell lines. Cell Immunol. 98, 341–350, 1986.
Brabant, M., McConlogue, Van Daalen Wetters, T. & Coffino, P. (1988). Mouse Ornithine decarboxylase gene: Cloning, structure and expression. Proc. Natl. Acad. Sci. USA 85, 2200–2204.
Coppolla, J.A. & Cole, M.D. (1986). Constitutive c-myc oncogene expression blocks mouse erythroleukemia cell differentiation but not commitment. Nature 320, 760–763.
Dean, M., Cleveland, J.L., Rapp, U. R., and Ihle, J. N. (1987). Role of myc in the abrogation of IL-3 dependence myeloid FDC-P1 cells. Oncogene Res. 1: 279–296.
Eilers, M., Schirm, S., and Bishop, J. M. (1991). The Myc protein activates transcription of the alphaprothymosin gene. EMBO J 10, 133–141.
Evan, G.I., Wylie, A.H., Gilbert, C.S., Littlewood, T., Land, H., Brooks, M., Waters, C.M., Penn, L.Z. and Hancock, D.C. (1992). Induction of apoptosis in fibroblasts by c-myc protein. Cell 69, 119–128.
Heikkela, R., Schwab, G., Wickstrom, E., Lohie, S., Pliznik, D.H., Watt, R. and Nacres, L. M. (1987). A c-myc antisense oligonucleotide inhibits entry into S phase but not progression from GO to G1. Nature 328, 445–449.
Halazonetis, T. D. and kandil, A. N. (1991). Determination of the c-myc DNA binding site. Proc. Natl. Acad. Sci. USA 88, 6162–6166.
Hibshoosh, H., Johnson, M. and Weinstein, I. B. (1991). Effects of overexpression of Ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation. Oncogene 6, 739–743.
Luscher, B. & Eisenman, R. (1990). New light on Myc and Myb. Part I: Myc. Genes Dev. 4: 2025–2035.
Kahana, C & Nathans, D. (1984). Nucleotide sequence of murine Ornithine decarboxylase mRNA. Proc. Natl. Acad. Sci. USA 81, 3645–3649.
Karn, J., Watson, J. V., Lowe, A. D., Greene, S. M. & Vedeck S, W. (1989). Regulation of cell cycle duration by c-myc levels. Oncogene 4, 773–781.
Kato, G. J., Barrett, J., Villa-Garcia, M. & Dang, C. V. (1990). An aminoterminal c-myc domain required for neoplastic transformation activates transcription. Mol. Cell. Biol. 10, 5914–5920.
Kato, G. J., Lee, W. M. F., Chen, L. & Dang, C. V. (1992). Max: Functional domains and interaction with c-myc. Genes Dev. 6, 81–92.
Katz, A. & kahana, C. (1988). Isolation and characterization of the mouse Ornithine decarboxylase gene. J. Biol. Chem. 263, 7604–7609.
Prendergast, G.C. & Ziff, E.B. (1991). Methylation-sensitive sequence-specific DNA binding by the c-myc basic region. Science 251, 186–189.
Prochownik, E.V. & kukowska, J.F. (1986). Deregulated expression of c-myc by murine erythroleukemia cells prevents differentiation. Nature 322, 848–850.
Prowchownik, E. V., kukowska, J. & Rodgers, C. (1988). c-myc antisense transcripts accelerate differentiation and inhibit G1 progression in murine erythroleukemia cells. Mol. Cell. Biol. 8, 3683–3695.
Rustgi, A. K., Dyson, N. & Bernards, R. (1991). Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product. Nature 352, 541–544.
Stone, J., De Lange, T., Ramsay, G., Jakobovis, E., Bishop, J. M., Varmus, H. & Lee, W. (1987). Definition of regions in human c-myc that are involved in transformation and nuclear translocation. Mol. Cell. Biol. 7, 1697–1709.
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© 1992 Springer-Verlag Berlin Heidelberg
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Bello-Fernandez, C., Cleveland, J.L. (1992). c-myc Transactivates the Ornithine Decarboxylase Gene. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1992. Current Topics in Microbiology and Immunology, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77633-5_56
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DOI: https://doi.org/10.1007/978-3-642-77633-5_56
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