Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1985 Nov;5(11):3009–3016. doi: 10.1128/mcb.5.11.3009

Regulation of the human c-myc gene: 5' noncoding sequences do not affect translation.

N Z Butnick, C Miyamoto, R Chizzonite, B R Cullen, G Ju, A M Skalka
PMCID: PMC369113  PMID: 3018494

Abstract

The influence of untranslated 5' sequences on c-myc expression was compared by measuring the translational efficiencies of mRNAs which contain leaders derived from exon 1 or intron 1 of the human c-myc gene. Expression plasmids were constructed and introduced into COS cells, and the levels of c-myc mRNA and protein were examined. Our results show that mRNAs transcribed from constructs containing exon 1 or intron 1, which have different folding potential, are translated with approximately equal efficiencies. This suggests that the translation of c-myc mRNA is not controlled by secondary structure alone. In addition, we observed that transcripts in which exon 1 was deleted are not translated more efficiently, but are present at a higher steady-state level. Thus, this example provides evidence for possible control at the transcriptional level. Finally, since the c-myc product was produced in each of our test systems, the results suggest that this protein does not regulate its own transcription or translation via a specific interaction with c-myc exon 1 alone.

Full text

PDF
3013

Images in this article

3012Image
on p.3012
3013Image
on p.3013
3014Image
on p.3014

Selected References

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

  1. Abrams H. D., Rohrschneider L. R., Eisenman R. N. Nuclear location of the putative transforming protein of avian myelocytomatosis virus. Cell. 1982 Jun;29(2):427–439. doi: 10.1016/0092-8674(82)90159-3. [DOI] [PubMed] [Google Scholar]
  2. Alitalo K., Ramsay G., Bishop J. M., Pfeifer S. O., Colby W. W., Levinson A. D. Identification of nuclear proteins encoded by viral and cellular myc oncogenes. Nature. 1983 Nov 17;306(5940):274–277. doi: 10.1038/306274a0. [DOI] [PubMed] [Google Scholar]
  3. Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell. 1983 Oct;34(3):779–787. doi: 10.1016/0092-8674(83)90534-2. [DOI] [PubMed] [Google Scholar]
  4. Berk A. J., Sharp P. A. Spliced early mRNAs of simian virus 40. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1274–1278. doi: 10.1073/pnas.75.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bernard O., Cory S., Gerondakis S., Webb E., Adams J. M. Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. EMBO J. 1983;2(12):2375–2383. doi: 10.1002/j.1460-2075.1983.tb01749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  7. Campisi J., Gray H. E., Pardee A. B., Dean M., Sonenshein G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. doi: 10.1016/0092-8674(84)90217-4. [DOI] [PubMed] [Google Scholar]
  8. Colby W. W., Chen E. Y., Smith D. H., Levinson A. D. Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29. Nature. 1983 Feb 24;301(5902):722–725. doi: 10.1038/301722a0. [DOI] [PubMed] [Google Scholar]
  9. Cullen B. R., Lomedico P. T., Ju G. Transcriptional interference in avian retroviruses--implications for the promoter insertion model of leukaemogenesis. Nature. 1984 Jan 19;307(5948):241–245. doi: 10.1038/307241a0. [DOI] [PubMed] [Google Scholar]
  10. Cullen B. R., Skalka A. M., Ju G. Endogenous avian retroviruses contain deficient promoter and leader sequences. Proc Natl Acad Sci U S A. 1983 May;80(10):2946–2950. doi: 10.1073/pnas.80.10.2946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dani C., Blanchard J. M., Piechaczyk M., El Sabouty S., Marty L., Jeanteur P. Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046–7050. doi: 10.1073/pnas.81.22.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Donner P., Greiser-Wilke I., Moelling K. Nuclear localization and DNA binding of the transforming gene product of avian myelocytomatosis virus. Nature. 1982 Mar 18;296(5854):262–269. doi: 10.1038/296262a0. [DOI] [PubMed] [Google Scholar]
  14. Dunnick W., Shell B. E., Dery C. DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7269–7273. doi: 10.1073/pnas.80.23.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eva A., Robbins K. C., Andersen P. R., Srinivasan A., Tronick S. R., Reddy E. P., Ellmore N. W., Galen A. T., Lautenberger J. A., Papas T. S. Cellular genes analogous to retroviral onc genes are transcribed in human tumour cells. Nature. 1982 Jan 14;295(5845):116–119. doi: 10.1038/295116a0. [DOI] [PubMed] [Google Scholar]
  16. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  17. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Graf T., Beug H. Avian leukemia viruses: interaction with their target cells in vivo and in vitro. Biochim Biophys Acta. 1978 Nov 17;516(3):269–299. doi: 10.1016/0304-419x(78)90011-2. [DOI] [PubMed] [Google Scholar]
  19. Hamlyn P. H., Rabbitts T. H. Translocation joins c-myc and immunoglobulin gamma 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature. 1983 Jul 14;304(5922):135–139. doi: 10.1038/304135a0. [DOI] [PubMed] [Google Scholar]
  20. Hann S. R., Abrams H. D., Rohrschneider L. R., Eisenman R. N. Proteins encoded by v-myc and c-myc oncogenes: identification and localization in acute leukemia virus transformants and bursal lymphoma cell lines. Cell. 1983 Oct;34(3):789–798. doi: 10.1016/0092-8674(83)90535-4. [DOI] [PubMed] [Google Scholar]
  21. Hann S. R., Eisenman R. N. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol. 1984 Nov;4(11):2486–2497. doi: 10.1128/mcb.4.11.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Keath E. J., Kelekar A., Cole M. D. Transcriptional activation of the translocated c-myc oncogene in mouse plasmacytomas: similar RNA levels in tumor and proliferating normal cells. Cell. 1984 Jun;37(2):521–528. doi: 10.1016/0092-8674(84)90382-9. [DOI] [PubMed] [Google Scholar]
  23. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
  26. Luthman H., Magnusson G. High efficiency polyoma DNA transfection of chloroquine treated cells. Nucleic Acids Res. 1983 Mar 11;11(5):1295–1308. doi: 10.1093/nar/11.5.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Müller R., Tremblay J. M., Adamson E. D., Verma I. M. Tissue and cell type-specific expression of two human c-onc genes. Nature. 1983 Aug 4;304(5925):454–456. doi: 10.1038/304454a0. [DOI] [PubMed] [Google Scholar]
  28. Nilsen T. W., Maroney P. A. Translational efficiency of cMyc mRNA in Burkitt lymphoma cells. Mol Cell Biol. 1984 Oct;4(10):2235–2238. doi: 10.1128/mcb.4.10.2235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Persson H., Leder P. Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. Science. 1984 Aug 17;225(4663):718–721. doi: 10.1126/science.6463648. [DOI] [PubMed] [Google Scholar]
  30. Rabbitts T. H., Hamlyn P. H., Baer R. Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma. Nature. 1983 Dec 22;306(5945):760–765. doi: 10.1038/306760a0. [DOI] [PubMed] [Google Scholar]
  31. Roussel M., Saule S., Lagrou C., Rommens C., Beug H., Graf T., Stehelin D. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature. 1979 Oct 11;281(5731):452–455. doi: 10.1038/281452a0. [DOI] [PubMed] [Google Scholar]
  32. Saito H., Hayday A. C., Wiman K., Hayward W. S., Tonegawa S. Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7476–7480. doi: 10.1073/pnas.80.24.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sheiness D., Bishop J. M. DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol. 1979 Aug;31(2):514–521. doi: 10.1128/jvi.31.2.514-521.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
  35. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  36. Stanton L. W., Watt R., Marcu K. B. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. doi: 10.1038/303401a0. [DOI] [PubMed] [Google Scholar]
  37. Taub R., Moulding C., Battey J., Murphy W., Vasicek T., Lenoir G. M., Leder P. Activation and somatic mutation of the translocated c-myc gene in burkitt lymphoma cells. Cell. 1984 Feb;36(2):339–348. doi: 10.1016/0092-8674(84)90227-7. [DOI] [PubMed] [Google Scholar]
  38. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Warden D., Thorne H. V. The infectivity of polyoma virus DNA for mouse embryo cells in the presence of diethylaminoethyl-dextran. J Gen Virol. 1968 Dec;3(3):371–377. doi: 10.1099/0022-1317-3-3-371. [DOI] [PubMed] [Google Scholar]
  40. Watson D. K., Psallidopoulos M. C., Samuel K. P., Dalla-Favera R., Papas T. S. Nucleotide sequence analysis of human c-myc locus, chicken homologue, and myelocytomatosis virus MC29 transforming gene reveals a highly conserved gene product. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3642–3645. doi: 10.1073/pnas.80.12.3642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Watt R., Nishikura K., Sorrentino J., ar-Rushdi A., Croce C. M., Rovera G. The structure and nucleotide sequence of the 5' end of the human c-myc oncogene. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6307–6311. doi: 10.1073/pnas.80.20.6307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Watt R., Stanton L. W., Marcu K. B., Gallo R. C., Croce C. M., Rovera G. Nucleotide sequence of cloned cDNA of human c-myc oncogene. Nature. 1983 Jun 23;303(5919):725–728. doi: 10.1038/303725a0. [DOI] [PubMed] [Google Scholar]
  43. Westin E. H., Wong-Staal F., Gelmann E. P., Dalla-Favera R., Papas T. S., Lautenberger J. A., Eva A., Reddy E. P., Tronick S. R., Aaronson S. A. Expression of cellular homologues of retroviral onc genes in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2490–2494. doi: 10.1073/pnas.79.8.2490. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES