Properties of the c-Myc Protein

  • Chi V. Dang
  • Linda A. Lee
Part of the Medical Intelligence Unit book series (MIU.LANDES)


Biology is full of surprises, and the regulation of c-myc readily illustrates this point. The regulation of c-myc expression is an intricate network of commands that controls transcriptional initiation, elongation as well as mRNA stability. In addition to this hierarchy of controls, production of the c-Myc polypeptides is also regulated. The predicted size of the c-myc encoded polypeptide initiated at the canonical AUG translational start site is 439 amino acids.1 The corresponding ATG is located at the 5' end of exon 2 (Fig. 4.1). Although the predicted molecular mass is 49.5 kDa, the observed size in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is about 62 kDa, which is largely due to the amino acid composition rather than to posttranslational modification.2–4 Hence this protein is termed p62Myc. From the same c-myc mRNAs, an alternative form of c-Myc polypeptide is translationally initiated at a CUG, 14 codons upstream from the canonical AUG (Fig. 6.1).5 This alternative form is termed p64Myc. These two forms of c-Myc appear as a doublet of polypeptides on SDS-PAGE.


Casein Kinase Nuclear Matrix Murine Erythroleukemia Cell Nuclear Colocalization Internal Translational Initiation Site 
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  1. 1.
    Watt R, Stanton LW, Marcu KB, Gallo RC, Croce CM, Rovera G. Nucleotide sequence of cloned cDNA of human c-myc oncogene. Nature 1983; 303: 725–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Ramsay G, Evan GI, Bishop JM. The protein encoded by the human proto-oncogene c-myc. Proc Natl Acad Sci USA 1984; 81: 7742–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Alitalo K, Ramsay G, Bishop JM, Pfeifer SO, Colby WW, Levinson AD. Identification of nuclear proteins encoded by viral and cellular myc oncogenes. Nature 1983; 306: 274–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Giallongo A, Appella E, Ricciardi R, Rovera G, Croce CM. Identification of the c-myc oncogene product in normal and malignant B cells. Science 1983; 222: 430–2.PubMedCrossRefGoogle Scholar
  5. 5.
    Hann SR, King MW, Bentley DL, Anderson CW, Eisenman RN. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt’s lymphomas. Cell 1988; 52: 185–95.PubMedCrossRefGoogle Scholar
  6. 6.
    Hann SR, Sloan-Brown K, Spotts GD. Translational activation of the non-AUG-initiated c-myc 1 protein at high cell densities due to methionine deprivation. Genes Dev 1992; 6: 1229–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Rabbitts PH, Watson JV, Lamond A, et al. Metabolism of c-myc gene products: c-myc mRNA and protein expression in the cell cycle. EMBO J 1985; 4: 2009–15.PubMedGoogle Scholar
  8. 8.
    Hann SR, Thompson CB, Eisenman RN. c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. Nature 1985; 314: 366–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Kato GJ, Barrett J, Villa-Garcia M, Dang CV. An amino-terminal c-myc domain required for neoplastic transformation activates transcription. Mol Cell Biol 1990; 10: 5914–20.PubMedGoogle Scholar
  10. 10.
    Blackwood EM, Lugo TG, Kretzner L, et al. Functional analysis of the AUG- and CUG-initiated forms of the c-Myc protein. Mol Biol Cell 1994; 5: 597–609.PubMedGoogle Scholar
  11. 11.
    Hann SR, Dixit M, Sears RC, Sealy L. The alternatively initiated c-Myc proteins differentially regulate transcription through a noncanonical DNA-binding site. Genes Dev 1994; 8: 2441–52.PubMedCrossRefGoogle Scholar
  12. 12.
    Luscher B, Eisenman RN. c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock. Mol Cell Biol 1988; 8: 2504–12.PubMedGoogle Scholar
  13. 13.
    Waters CM, Littlewood TD, Hancock DC, Moore JP, Evan GI. c-myc protein expression in untransformed fibroblasts. Oncogene 1991; 6: 797–805.PubMedGoogle Scholar
  14. 14.
    Moore JP, Hancock DC, Littlewood TD, Evan GI. A sensitive and quantitative enzyme-linked immunosorbence assay for the c-myc and N-myc oncoproteins. Oncogene Res 1987; 2: 65–80.PubMedGoogle Scholar
  15. 15.
    Spotts GD, Hann SR. Enhanced translation and increased turnover of c-myc proteins occur during differentiation of murine erythroleukemia cells. Mol Cell Biol 1990; 10: 3952–64.PubMedGoogle Scholar
  16. 16.
    Wingrove TG, Watt R, Keng P, Macara IG. Stabilization of myc proto-oncogene proteins during Friend murine erythroleukemia cell differentiation. J Biol Chem 1988; 263: 8918–24.PubMedGoogle Scholar
  17. 17.
    Rogers S, Wells R, Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 1986; 234: 364–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Ciechanover A, DiGiuseppe JA, Bercovich B, et al. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci USA 1991; 88: 139–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Luscher B, Eisenman RN. Proteins encoded by the c-myc oncogene: analysis of c-myc protein degradation. Princess Takamatsu Symp 1986; 17: 291–301.PubMedGoogle Scholar
  20. 20.
    Hann SR, Eisenman RN. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol 1984; 4: 2486–97.PubMedGoogle Scholar
  21. 21.
    Persson H, Gray HE, Godeau F, Braunhut S, Bellve AR. Multiple growth-associated nuclear proteins immunoprecipitated by antisera raised against human c-myc peptide antigens. Mol Cell Biol 1986; 6: 942–9.PubMedGoogle Scholar
  22. 22.
    Ramsay G, Hayman MJ, Bister K. Phosphorylation of specific sites in the gag-myc polyproteins encoded by MC29-type viruses correlates with their transforming ability. EMBO J 1982; 1: 1111–6.PubMedGoogle Scholar
  23. 23.
    Hagiwara T, Nakaya K, Nakamura Y, Nakajima H, Nishimura S, Taya Y. Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II. Eur J Biochem 1992; 209: 945–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Bousset K, Oelgeschlager MHH, Henriksson M, et al. Regulation of transcription factors c-Myc, Max, and c-Myb by casein kinase II. Cell Molec Biol Res 1995; 40: 501–511.Google Scholar
  25. 25.
    Luscher B, Kuenzel EA, Krebs EG, Eisenman RN. Myc oncoproteins are phosphorylated by casein kinase II. EMBO J 1989; 8: 1111–9.PubMedGoogle Scholar
  26. 26.
    Lutterbach B, Hann SR. Hierarchical phosphorylation at n-terminal transformation-sensitive sites in c-myc protein is regulated by mitogens and in mitosis. Mol Cell Biol 1994; 14: 5510–22.PubMedGoogle Scholar
  27. 27.
    Seth A, Alvarez E, Gupta S, Davis RJ. A phosphorylation site located in the NH2-terminal domain of c-Myc increases trans-activation of gene expression. J Biol Chem 1991; 266: 23521–4.PubMedGoogle Scholar
  28. 28.
    Gupta S, Seth A, Davis R. Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62. Proc Natl Acad Sci, USA 1993; 90: 3216–20.CrossRefGoogle Scholar
  29. 29.
    Jackson SP. Regulating transcription factor activity by phosphorylation. TICB 1992; 2: 104–8.CrossRefGoogle Scholar
  30. 30.
    Iijima S, Teraoka H, Date T, Tsukada K. DNA-activated protein kinase in Raji Burkitt’s lymphoma cells. Phosphorylation of c-Myc oncoprotein. Eur J Biochem 1992; 206: 595–603.PubMedCrossRefGoogle Scholar
  31. 31.
    Seldin DC, Leder P. Casein kinase II alpha transgene-induced murine lymphoma: relation to theileriosis in cattle [see comments]. Science 1995; 267: 894–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Berberich SJ, Cole MD. Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers. Genes Dev. 1992; 6: 166–76.PubMedCrossRefGoogle Scholar
  33. 33.
    Bousset K, Henriksson M, Luscherfirzlaff JM, Litchfield DW, Luscher B. Identification of casein kinase ii phosphorylation sites in max–effects on dna-binding kinetics of max homo-and myc/ max heterodimers. Oncogene 1993; 8: 3211–20.PubMedGoogle Scholar
  34. 34.
    Seth A, Gupta S, Davis RJ. Cell cycle regulation of the c-Myc transcriptional activation domain. Mol Cell Biol 1993; 13: 4125–36.PubMedGoogle Scholar
  35. 35.
    Henriksson M, Bakardjiev A, Klein G, Luscher B. Phosphorylation sites mapping in the N-terminal domain of c-myc modulate its transforming potential. Oncogene 1993; 8: 3199–209.PubMedGoogle Scholar
  36. 36.
    Pulverer BJ, Fisher C, Vousden K, Littlewood T, Evan G, Woodgett JR. Site-specific modulation of c-myc cotransformation by residues phosphorylated in vivo. Oncogene 1994; 9: 59–70.PubMedGoogle Scholar
  37. 37.
    Hoang AT, Lutterbach B, Lewis BC, et al. A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain. Mol Cell Biol 1995; 15: 4031–42.PubMedGoogle Scholar
  38. 38.
    Chou TY, Dang CV, Hart GW. Glycosylation of the c-Myc transactivation domain. Proc Natl Acad Sci USA 1995; 92: 4417–21.PubMedCrossRefGoogle Scholar
  39. 39.
    Chou TY, Hart GW, Dang CV. c-Myc is glycosylated at threonine-58, a known phosphorylation site and a mutational hot spot in lymphomas. J Biol Chem 1995; 270.Google Scholar
  40. 40.
    Hann SR, Abrams HD, Rohrschneider LR, Eisenman RN. Proteins encoded by v-myc and c-myc oncogenes: identification and localization in acute leukemia virus transformants and bursal lymphoma cell lines. Cell 1983; 34: 789–98.PubMedCrossRefGoogle Scholar
  41. 41.
    Abrams HD, Rohrschneider LR, Eisenman RN. Nuclear location of the putative transforming protein of avian myelocytomatosis virus. Cell 1982; 29: 427–39.PubMedCrossRefGoogle Scholar
  42. 42.
    Bunte T, Greiser-Wilke I, Donner P, Moelling K. Association of gag-myc proteins from avian myelocytomatosis virus wild-type and mutants with chromatin. EMBO J 1982; 1: 919–27.PubMedGoogle Scholar
  43. 43.
    Bunte T, Greiser-Wilke I, Moelling K. The transforming protein of the MC29-related virus CMII is a nuclear DNA-binding protein whereas MH2 codes for a cytoplasmic RNA-DNA binding polyprotein. EMBO J 1983; 2: 1087–92.PubMedGoogle Scholar
  44. 44.
    Persson H, Leder P. Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. Science 1984; 225: 718–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Spector DL, Watt RA, Sullivan NF. The v-and c-myc oncogene proteins colocalize in situ with small nuclear ribonucleoprotein particles. Oncogene 1987; 1: 5–12.PubMedGoogle Scholar
  46. 46.
    Craig RW, Buchan HL, Civin CI, Kastan MB. Altered cytoplasmic/nuclear distribution of the c-myc protein in differentiating ML-1 human myeloid leukemia cells. Cell Growth Differ 1993; 4: 349–57.PubMedGoogle Scholar
  47. 47.
    Gusse M, Ghysdael J, Evan G, Soussi T, Mechali M. Translocation of a store of maternal cytoplasmic c-myc protein into nuclei during early development. Mol Cell Biol 1989; 9: 5395–403.PubMedGoogle Scholar
  48. 48.
    Vriz S, Lemaitre JM, Leibovici M, Thierry N, Mechali Error! Hyperlink reference not valid.parative analysis of the intracellular localization of c-Myc, c-Fos, and replicative proteins during cell cycle progression. Mol Cell Biol 1992; 12: 3548–55.PubMedGoogle Scholar
  49. 49.
    King MW, Roberts JM, Eisenman RN. Expression of the c-myc proto-oncogene during development of Xenopus laevis. Mol Cell Biol 1986; 6: 4499–508.PubMedGoogle Scholar
  50. 50.
    Eisenman RN, Tachibana CY, Abrams HD, Hann SR. V-mycand c-myc-encoded proteins are associated with the nuclear matrix. Mol Cell Biol 1985; 5: 114–26.PubMedGoogle Scholar
  51. 51.
    Van Straaten JP, Rabbitts TH. The c-myc protein is associated with the nuclear matrix through specific metal interaction. Oncogene Res 1987; 1: 221–8.PubMedGoogle Scholar
  52. 52.
    Evan GI, Hancock DC. 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. Cell 1985; 43: 253–61.PubMedCrossRefGoogle Scholar
  53. 53.
    Koskinen PJ, Sistonen L, Evan G, Morimoto R, Alitalo K. Nuclear colocalization of cellular and viral myc proteins with HSP70 in myc-overexpressing cells. J Virol 1991; 65: 842–51.PubMedGoogle Scholar
  54. 54.
    Henriksson M, Classon M, Axelson H, Klein G, Thyberg J. Nuclear colocalization of c-myc protein and hsp70 in cells transfected with human wild-type and mutant c-myc genes. Exp Cell Res 1992; 203: 383–94.PubMedCrossRefGoogle Scholar
  55. 55.
    Henriksson M, Classon M, Ingvarsson S, et al. Elevated expression of c-myc and N-myc produces distinct changes in nuclear fine structure and chromatin organization. Oncogene 1988; 3: 587–93.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Chi V. Dang
    • 1
  • Linda A. Lee
    • 1
  1. 1.School of MedicineThe Johns Hopkins UniversityBaltimoreUSA

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