The myc oncoproteins are expressed in a wide range of normal adult and embryonic tissues. They are also found to be over-expressed in a variety of tumor types. All myc proteins are short-lived nuclear phosphoproteins thought to act as regulatory components of cell proliferation. The rapid induction of c- myc mRNA and protein following the addition of growth factors to quiescent cells, together with the short half-life of these molecules, suggests that they are sensitive and continuous indicators of external stimuli, consistent with a role in signal transduction. Furthermore, in untransformed cells, c-myc protein expression is tightly regulated, at least in part, by a mechanism of autoregulation. Deregulated expression of myc genes is a frequent observation in tumors and may lead to a cell becoming independent of one or more growth factors, with the concomitant potential for uncontrolled proliferation. Although the precise functions of the myc proteins are unknown, they all bear the hallmarks of multimeric DNA-binding proteins probably involved in the regulation of expression of specific genes.
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References
1.
Adams, J.; Gerondakis, S.; Webb, E.; Corcoran, L.M.; and Cory, S. (1983): Cellular myc Oncogene is Altered by Chromosomal Translocation to the Immunoglobulin Locus in Murine Plasmacytomas and is Rearranged Similarly in Human Burkitt Lymphomas, Proc Natl Acad Sci USA80: 1982-1986.
2.
Alitalo, K. and Schwab, M. (1986): Oncogene Amplification in Tumor Cells, Adv Cancer Res47: 235-281.
3.
Almendral, J.M.; Sommer, D.; MacDonald-Bravo, H.; Burckhardt, J.; Perera, J.; and Bravo, R. (1988): Complexity of the Early Genetic Response to Growth Factors in Mouse Fibroblasts, Molec Cell Biol8: 2140-2148.
4.
Alonso, M.C. and Cabrera, C.V. (1988): The achaete-scute Gene Complex of Drosophila Melanogaster Comprises Four Homologous Genes, EMBO J7: 2585-2591.
5.
Beard, J.W.; Chabot, J.F.; Beard, D.; Heine, U.; and Houts, G.E. (1976): Renal Neoplastic Response to Leukosis Virus Strain BAIA (avian myeloblastosis virus) and MC29, Cancer Res36: 339-353.
6.
Beard, J.W.; Hillman, E.A.; Beard, D.; Lapis, K.; and Heine, U. (1975): Neoplastic Response of the Avian Liver to Host Infection with MC29 Leukosis Virus, Cancer Res35: 1603-1627.
7.
Bernard, 0.; Cory, S.; Gerondakis, S.; Webb, S.; and Adams, J.M. (1983): Sequence of the Murine and Human Cellular myc Oncogenes and Two Modes of Myc Transcription Resulting from Chromosome Translocation in B Lymphoid Tumors , EMBO J2: 2375-2383.
8.
Bister, K.; Ramsay, G.; and Hayman, M.J. (1982): Deletions within the Transformation-specific RNA Sequences of Acute Leukemia Virus MC29 Give Rise to Partially Transformation-defective Mutants, J Virol41: 754-766.
9.
Braun, H.M.; Buschhausen-Denker, G.; Bober, E.; and Arnold, H.H. (1989): A Novel Human Muscle Factor Related to, but Distinct from, MyoDl Induces Myogenic Conversion in 10T1/2 Fibroblasts, EMBO J8: 701-709.
10.
Campisi, J.; Gray, H.E.; Pardee, A.B.; Dean, M.; and So-Nenshein, G.E. (1984): Cell-Cycle Control of C-myc but not C-ras Expression is Lost Following Chemical Transformation, Cell36: 241-247.
11.
Caudy, M.; Vassin, H.; Brand, M.; Tuma, R.; Jan, L.Y.; and Jan, Y.N. (1988): Daughterless, a Gene Essential for Both Neurogenesis and Sex Determination, has Sequence Similarities to myc and the achaete-scute Complex, Cell55: 1061-1067.
12.
Cochran, B.H.; Zullo, J.; Verma, I.M.; and Stiles, C.D. (1984): Expression of the c-fos Gene and of an fos-related Gene is Stimulated by Platelet-derived Growth Factor, Science226 : 1080-1082.
13.
Colby, W.W.; Chen, E.Y.; Smith, D.H.; and Levinson, A.D. (1983): Identification and Nucleotide Sequence of a Human Locus Homologous to the c-myc Oncogene of Avian Myelocytomatosis Virus MC29 , Nature (London)301: 722-725.
14.
Coppola, J.A. and Cole, M.D. (1986): Constitutive c-myc Oncogene Expression Blocks Mouse Erythroleukemia Cell Differentiation but not Commitment, Nature (London)320: 760-763.
15.
Crews, S.; Barth, R.; Hood, L.; Prehn, J.; and Calame, K. (1982): Mouse c-myc Oncogene is Located on Chromosome 15 and Translocated to Chromosome 12 in Plasmacytomas, Science218: 1319-1321.
16.
Dalla Favera, R.; Bregni, M.; Erikson, J.; Patterson, D.; Gallo, R.C.; and Croce, C.M. (1982a): Human c-myc onc Gene is Located on the Region of Chromosome 8 that is Translocated in Burkitt Lymphoma Cells, Proc Natl Acad Sci USA79: 7824-7827.
17.
Dalla Favera, R.; Gelmann, E.P.; Martinoti, S.; Fran-Chini, G.; Papas, T.S.; Gallo, R.C.; and Wong-Staal, F. (1982b): Cloning and Characterization of Different Human Sequences Related to the onc Gene (v-myc) of Avian Myelocytomatosis Virus (MC29), Proc Natl Acad Sci USA79: 6497-6501.
18.
Dang, C. and Lee, W.M.F. (1988): Identification of the Human c-myc Protein Nuclear Translocation Signal, Molec Cell Biol8: 4048-4054.
19.
Davis, R.L.; Weintraub, H.; and Lassar, A.B. (1987): Expression of a Single Transfected cDNA Converts Fibroblasts to Myoblasts, Cell51: 987-1000.
20.
De Greve, J.; Battey, J.; Fedorko, J.; Birrer, M.; Evan, G.; Kaye, F.; Ausville, E.; and Minna, J. (1988): The Human L-myc Gene Encodes Multiple Nuclear Phosphoproteins from Alternatively Processed mRNAs, Molec Cell Biol8: 4381-4388.
21.
Dean, M.; Levine, R.A.; Ran, W.; Kindy, M.S.; Sonen-Shein, G.E.; and Campisi, J. (1986): Regulation of c-myc Transcription and mRNA Abundance by Serum Growth Factors and Cell Contact, J Biol Chem261: 9161-9166.
22.
Depinho, R.A.; Hatton, K.S.; Tesfaye, A.; Yancopoulos, G.D.; and Alt, F.W. (1987): The Human myc Gene Family : Structure and Activity of L-myc and an L-myc Pseudogene, Genes Develop1: 1311-1326.
23.
Dmitrovsky, E.; Kuehl, W.M.; Hollis, G.F.; Kirsch, I.R.; Bender, T.P.; and Segal, S. (1986): Expression of a Transfected Human c-myc Oncogene Inhibits Differentiation of a Mouse Erythroleukemia Cell Line, Nature (London)322: 748-750.
24.
Erisman, M.D. and Astrin, S.M. (1988): The myc Oncogene. In: The Oncogene Handbook, E.P. Reddy, A.M. Skalka, and T. Curran , Eds., Amsterdam. New York , London: Elsevier Science Publishers, pp. 341-379.
25.
Evan, G.I. and Hancock, D.C. (1985): Studies on the Interaction of the Human c-myc Protein with Cell Nuclei: p62c-myc as a Member of a Discrete Subset of Nuclear Proteins, Cell43: 253-261.
26.
Evan, G.I.; Hancock, D.C.; Littlewood, T.D.; and Gee, N.S. (1986): Characterisation of Human myc Proteins, Curr Top Microbiol Immunol132: 362-374.
27.
Evan, G.I.; Moore, J.P.; Ibson, J.M.; Waters, C.M.; Hancock, D.C.; and Littlewood, T.D. (1988): Immunological Probes in the Analysis of myc Protein Expression, Curr Top Microbiol Immunol141: 189-201.
28.
Field, J.K.; Spandidos, D.A.; Stell, P.M.; Vaughan, E.D.; Evan, G.I.; and Moore, J.P. (1989): Elevated Expression of the c-myc Oncoprotein Correlates with Poor Prognosis in Head and Neck Squamous Cell Carcinoma, Oncogene4: 1463-1468.
29.
Figge, J.; Webster, T.; Smith, T.F.; and Paucha, E. (1988): Prediction of Similar Transforming Regions in Simian Virus 40 Large T, Adenovirus E1A and myc Oncoproteins, J Virol62: 1814-1818.
30.
Freytag, S.O. (1988): Enforced Expression of the c-myc Oncogene Inhibits Cell Differentiation by Precluding Entry into a Distinct Predifferentiation State in G0/G1, Molec Cell Biol8 : 1614-1624.
31.
Greenberg, M.E. and Ziff, E.B. (1984): Stimulation of 3T3 Cells Induces Transcription of the c-fos Proto-oncogene, Nature (London)311: 433-438.
32.
Hann, S.R. and Eisenman, R.N. (1984): Proteins Encoded by the Human c-myc Oncogene: Differential Expression in Neoplastic Cells, Molec Cell Biol4: 2486-2497.
33.
Hann, S.R.; King, M.W.; Bentley, D.L.; Anderson, C.W.; and Eisenman, R.N. (1988): A Non-AUG Translational Initiation in c-myc Exon 1 Generates an N-terminally Distinct Protein whose Synthesis is Disrupted in Burkitt's Lymphomas, Cell52: 185-195.
34.
Hann, S.R.; Thompson, C.B.; and Eisenman, R.N. (1985): C-myc Oncogene Protein Synthesis is Independent of the Cell Cycle in Human and Avian Cells, Nature (London)314: 366-369.
35.
Hayward, W.; Neel, B.G.; and Astrin, S. (1981): Activation of a Cellular onc Gene by Promoter Insertion in ALV-induced Lymphoid Leukosis, Nature290: 475-480.
36.
Kelly, K.; Cochran, B.H.; Stiles, C.D.; and Leder, P. (1983): Cell Specific Regulation of the c-myc Gene by Lymphocyte Mitogens and Platelet-derived Growth Factor, Cell35: 603-610.
37.
Land, H.; Parada, L.F.; and Weinberg, R.A. (1983): Tumorigenic Conversion of Primary Embryo Fibroblasts Requires at Least Two Cooperating Oncogenes, Nature (London)304: 596-602.
38.
Landschulz, W.H.; Johnson, P.F.; and McKnight, S.L. (1988): The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins, Science240: 1759-1764.
39.
Levy, L.S.; Gardner, M.B.; and Casey, J.W. (1984): Isolation of a Feline Leukemia Provirus Containing the Oncogene myc from a Feline Lymphosarcoma, Nature (London)308: 853-856.
40.
Luscher, B.; Kuenzel, E.A.; Krebs, E.G.; and Eisenman, R.N. (1989): Myc Oncoproteins are Phosphorylated by Casein Kinase II, EMBO J8: 1111-1119.
41.
Makela, T.P.; Saksela, K.; and Alitalo, K. (1989): Two N-myc Polypeptides with Distinct Amino Termini Encoded by the Second and Third Exons of the Gene, Molec Cell Biol9: 1545-1552.
42.
Marcu, K.B. (1987): Regulation of Expression of the c-myc Proto-oncogene , BioEssays6: 28-32.
43.
Marcu, K.B.; Harris, L.J.; Stanton, L.W.; Erikson, J.; Watt, R.; and Croce, C.M. (1983): Transcriptionally Active c-myc Oncogene is Contained within NIARD, a DNA Sequence Associated with Chromosome Translocation in B-cell Neoplasia, Proc Natl Acad Sci USA80: 519-524.
44.
Martinsson, T.; Stahl, F.; Pollwein, P.; Wenzel, A.; Levan, A.; Schwab, M.; and Levan, G. (1988): Tumorigenicity of SEWA Murine Cells Correlates with Degree of c-myc Amplification, Oncogene3: 437-441.
45.
Mladenov, T.; Heine, U.; Beard, D.; and Beard, J.W. (1967): Strain MC29 of Avian Leukosis Virus. Myelocytoma, Endothelioma, and Renal Growths: Pathomorphological and Ultrastructural Aspects, J Natl Cancer Inst38: 251-285.
46.
Moore, J.P.; Hancock, D.C.; Littlewood, T.D.; and Evan, G.I. (1987): A Sensitive and Quantitative Enzyme-linked Immunosorbence Assay for the c-myc and N-myc Oncoproteins, Oncogene Res2: 65-80.
47.
Mullins, J.I.; Brody, D.S.; Binari, R.C.; and Cotter, S.M. (1984): Viral Transduction of c-myc Gene in Naturally Occurring Feline Leukemias, Nature (London)308: 856-858.
48.
Murre, C.; McCaw, P.S.; and Baltimore, D. (1989): A New DNA Binding and Dimerization Motif in Immunoglobulin Enhancer Binding daughterless, MyoD, and myc Proteins, Cell56: 777-783.
49.
Nau, M.M.; Brooks, B.J.; Battey, J.; Sausville, E.; Gaz-Dar, A.F.; Kirsch, I.R.; McBride, O.W.; Bertness, V.; Hollis, G.F.; and Minna, J.D. (1985): L-myc, a New mycrelated Gene Amplified and Expressed in Human Small Cell Lung Cancer, Nature (London)318: 69-73.
50.
Neel, B.G.; Jhanwar, S.C.; Chaganti, R.S.K.; and Hayward, W.S. (1982): Two Human onc Genes are Located on the Long Arm of Chromosome 8, Proc Natl Acad Sci USA79: 7842-7846.
51.
Neil, J.C.; Hughes, D.; MacFarlene, R.; Wilkie, N.M.; Onions, D.E.; Lees, G.; and Jarret, O. (1984): Transduction and Rearrangement of the myc Gene by Feline Leukemia Virus in Naturally Occurring T-cell Leukemias, Nature (London)308: 814-820.
52.
Payne, G.S.; Bishop, J.M.; and Varmus, H.E. (1982): Multiple Arrangements of Viral DNA and Host Oncogene in Bursal Lymphomas, Nature (London)295: 209-214.
53.
Persson, H.; Hennighausen, L.; Taub, R.; Degrado, W.; and Leder, P. (1984): Antibodies to Human c-myc Oncogene Product: Evidence of an Evolutionarily Conserved Protein Induced During Cell Proliferation, Science225: 687-693.
54.
Persson, H. and Leder, P. (1984): Nuclear Localization and DNA Binding Properties of a Protein Expressed by Human c-myc Oncogenes, Science225: 718-721.
55.
Pinney, D.F.; Pearson-White, S.H.; Konieczny, S.F.; La-Tham, K.E.; and Emerson, C.P. (1988): Myogenic Lineage Determination and Differentiation: Evidence for a Regulatory Gene Pathway, Cell53: 781-793.
56.
Prochownik, E.V. and Kukowsa, J. (1986): Deregulated Expression of c-myc by Murine Erythroleukemia Cells Prevents Differentiation, Nature (London)322: 848-850.
57.
Ramsay, G.M.; Enrietto, P.S.; Graf, T.; and Hayman, M.J. (1982): Recovery of myc-specific Sequences by a Partially Transformation-defective Mutant of Avian Myelocytomatosis Virus, MC29, Correlates with the Restoration of Transforming Activity, Proc Natl Acad Sci USA79: 6885-6889.
58.
Ramsay, G.; Evan, G.I.; and Bishop, J.M. (1984): The Protein Encoded by the Human Proto-oncogene c-myc, Proc Natl Acad Sci USA81: 7742-7746.
59.
Ramsay, G.; Graf, T.; and Hayman, M.J. (1980): Mutants of Avian Myelocytomatosis Virus with Smaller gag Gene-related Proteins have an Altered Transforming Ability, Nature (London)288: 170-172.
60.
Ramsay, G.M. and Hayman, M.J. (1982): Isolation and Characterisation of Partially Transformation-defective Mutants of Avian Myelocytomatosis Virus Strain MC29: Localization of the Mutation to the Myc Domain of the 110,000-dalton gag-myc Polyprotein, J Virol41: 745-753.
61.
Ramsay, G.; Stanton, L.; Schwab, M.; and Bishop, J.M. (1986): N-myc Encodes a Nuclear Protein that Binds to DNA, Molec Cell Biol6: 4450-4457.
62.
Robins, T.; Bister, K.; Garon, C.; Papas, T.; and Dues-Berg, P. (1982): Structural Relationship Between a Normal Chicken DNA Locus and the Transforming Gene of the Acute Avian Leukemia Virus MC29 , J Virol41: 635-642.
63.
Saksela, K.; Makela, T.P.; Evan, G.; and Alitalo, K. (1989): Rapid Phosphorylation of the L-myc Protein Induced by Phorbol Ester Tumor Promoters and Serum, EMBO J8: 149-158.
64.
Sarid, J.; Halazonetis, T.D.; Murphy, W.; and Leder, P. (1987): Evolutionarily Conserved Regions of the Human c-myc Protein can be Uncoupled from Transforming Activity, Proc Natl Acad Sci USA84: 170-173.
65.
Schwab, M. (1985): Amplification of N-myc in Human Neuroblastomas , Trends Genet1: 271-275.
66.
Schwab, M. (1988): The myc-box Oncogenes. In The Oncogene Handbook, E.P. Reddy, A.M. Skalka, and T. Curran , Eds., Amsterdam, New York , London: Elsevier Science Publishers, pp. 381-391.
67.
Seeger, R.C.; Brodeur, G.M.; Sather, H.; Dalton, A.; Siegel, S.E.; Wong, K.Y.; and Hammond, D. (1985): Association of Multiple Copies of the N-myc Oncogene with Rapid Progression of Neuroblastomas, N Engl J Med313: 1111-1116.
68.
Shen-Ong. G.L.C.; Keath, E.J.; Piccoli, S.P.; and Cole, M.D. (1982): Novel myc Oncogene RNA from Abortive Immunoglobulin-gene Recombination in Mouse Plasmacytomas, Cell31: 443-452.
69.
Slamon, D.J.; Boone, T.C.; Seeger, R.C.; Keith, D.E.; Chaziu, V.; Lee, H.C.; and Souza, L.M. (1986): Identification and Characterization of the Protein Encoded by the Human N-myc Oncogene, Science232: 768-772.
70.
Small, M.B.; Hay, N.; Schwab, M.; and Bishop, J.M. (1987): Neoplastic Transformation by the Human Gene N-myc , Molec Cell Biol7: 1638-1645.
71.
Stone, J.; DE Lange, T.; Ramsay, G.; Jakobvits, E.; Bishop, J.M.; Varmus, H.; and Lee, W. (1987): Definition of Regions in Human c-myc that are Involved in Transformation and Nuclear Localization, Molec Cell Biol7: 1697-1709.
72.
Taub, R.; Moulding, C.; Battey, J.; Murphy, W.; Vasi-Cek, T.; Lenoir, G.M.; and Leder, P. (1984): Activation and Somatic Mutation of the Translocated c-myc gene in Burkitt Lymphoma Cells, Cell36: 339-348.
73.
Taylor, M.V.; Gusse, M.; Evan, G.I.; Dathan, N.; and Mechali, M. (1986): Xenopus myc Proto-oncoprotein Expression During Development: Expression as a Stable Maternal mRNA Uncoupled from Cell Division , EMBO J5: 3563-3570.
74.
Thisse, B.; Stoetzel, C.; Gorostiza-Thisse, C.; and Perrin-Schmitt, F. (1988): Sequence of the twist Gene and Nuclear Localization of its Protein in Endomesodermal Cells of Early Drosophila Embryos, EMBO J7: 2175-2183.
75.
Van Beneden, R.J.; Watson, D.K.; Chen, T.T.; Lautenberger, J.A.; and Papas, T.S. (1986): Cellular myc (c-myc) in Fish Rainbow Trout: its Relationship to Other Vertebrate Myc Genes and to the Transforming Gene of the MC29 Family of Viruses, Proc Natl Acad Sci USA83: 3698-3702.
76.
Vennstrom, B.; Sheiness, D.; Zabielski, J.; and Bishop, J.M. (1982): Isolation and Characterization of c-myc, a Cellular Homolog of the Oncogene (v-myc) of Avian Myelocytomatosis Virus Strain 29 , J Virol42: 773-779.
77.
Watson, D.K.; Psallidopoulos, M.C.; Samuel, K.P.; Dalla Favera, R.; and Papas, T.S. (1983): Nucleotide Sequence Analysis of Human c-myc Locus, Chicken Homologue, and Avian Myelocytomatosis Virus MC29 Transforming Gene Reveals a Highly Conserved Gene Product, Proc Natl Acad Sci USA80: 3642-3645.
78.
Watt, R.A.; Schatzman, A.R.; and Rosenberg, M. (1985): Expression and Characterization of the Human c-myc DNA-Binding Protein, Molec Cell Biol5: 448-456.
79.
Westin, L.; Wong-Staal, F.; Gelmann, E.; Dalla Favera, R.; Papas, T.; Lautenberger, J.; Eva, A.; Reddy, E.; Tronick, S.; Aaronson, S.; and Gallo, R. (1982): Expression of Cellular Homologues of Retroviral Oncogenes in Human Haematopoietic Cells, Proc Natl Acad Sci USA79: 2490-2494.
80.
Wright, W.E.; Sassoon, D.A.; and Lin, V.K. (1989): Myogenin, a Factor Regulating Myogenesis, has a Domain Homologous to MyoD, Cell56: 607-617.
81.
Yancopoulos, G.D.; Nisen, P.D.; Tesfaye, A.; Kohl, N.E.; Goldfarb, M.P.; and Alt, F.W. (1985): N-myc can Cooperate with ras to Transform Normal Cells in Culture, Proc Natl Acad Sci USA8: 5455-5459.
