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. 1992 Nov;66(11):6773–6776. doi: 10.1128/jvi.66.11.6773-6776.1992

Protein truncation is not required for c-myb proto-oncogene activity in neuroretina cells.

C Garrido 1, F Grässer 1, J S Lipsick 1, D Stehelin 1, S Saule 1
PMCID: PMC240175  PMID: 1404616

Abstract

The v-myb oncogene of avian myeloblastosis virus (AMV) differs from its normal cellular counterpart by a truncation at both its amino and carboxyl termini and by a substitution of 11 amino acid residues. We had previously shown that v-myb-containing AMV, in the presence of basic fibroblast growth factor, transformed chicken neuroretina (CNR) cells. To understand the mechanism of c-myb activation, we have tested whether avian retroviruses that express the full-length c-Myb are also active on CNR cells. We have found that c-Myb, like v-Myb, strongly increases the basic fibroblast growth factor response of CNR cells and that these c-myb-expressing cells are able to grow in soft agar in the presence of the growth factor. We have also found that, in contrast to normal or v-myb-expressing AMV-transformed CNR cells, c-Myb-transformed cells express mim-1, a granulocyte-specific gene. However, normal v-Myb- and c-Myb-expressing CNR cells all express the pax-QNR gene, a newly described paired and homeobox-containing gene specifically expressed in the neuroretina. We conclude that, in contrast to what has been described for hematopoietic cells, overexpression of c-Myb is sufficient to activate gene expression and to induce an abnormal behavior of CNR cells.

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Selected References

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  1. Biedenkapp H., Borgmeyer U., Sippel A. E., Klempnauer K. H. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. doi: 10.1038/335835a0. [DOI] [PubMed] [Google Scholar]
  2. Boyle W. J., Lampert M. A., Lipsick J. S., Baluda M. A. Avian myeloblastosis virus and E26 virus oncogene products are nuclear proteins. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4265–4269. doi: 10.1073/pnas.81.14.4265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyle W. J., Lipsick J. S., Reddy E. P., Baluda M. A. Identification of the leukemogenic protein of avian myeloblastosis virus and of its normal cellular homologue. Proc Natl Acad Sci U S A. 1983 May;80(10):2834–2838. doi: 10.1073/pnas.80.10.2834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clarke M. F., Kukowska-Latallo J. F., Westin E., Smith M., Prochownik E. V. Constitutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation. Mol Cell Biol. 1988 Feb;8(2):884–892. doi: 10.1128/mcb.8.2.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coll J., Saule S., Martin P., Raes M. B., Lagrou C., Graf T., Beug H., Simon I. E., Stehelin D. The cellular oncogenes c-myc, c-myb and c-erb are transcribed in defined types of avian hematopoietic cells. Exp Cell Res. 1983 Nov;149(1):151–162. doi: 10.1016/0014-4827(83)90388-9. [DOI] [PubMed] [Google Scholar]
  6. Erba H. P., Gunning P., Kedes L. Nucleotide sequence of the human gamma cytoskeletal actin mRNA: anomalous evolution of vertebrate non-muscle actin genes. Nucleic Acids Res. 1986 Jul 11;14(13):5275–5294. doi: 10.1093/nar/14.13.5275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Garrido C., Leprince D., Lipsick J. S., Stehelin D., Gospodarowicz D., Saule S. Definition of functional domains in P135gag-myb-ets and p48v-myb proteins required to maintain the response of neuroretina cells to basic fibroblast growth factor. J Virol. 1992 Jan;66(1):160–166. doi: 10.1128/jvi.66.1.160-166.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gerondakis S., Bishop J. M. Structure of the protein encoded by the chicken proto-oncogene c-myb. Mol Cell Biol. 1986 Nov;6(11):3677–3684. doi: 10.1128/mcb.6.11.3677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gospodarowicz D., Cheng J., Lui G. M., Baird A., Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6963–6967. doi: 10.1073/pnas.81.22.6963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grässer F. A., Graf T., Lipsick J. S. Protein truncation is required for the activation of the c-myb proto-oncogene. Mol Cell Biol. 1991 Aug;11(8):3987–3996. doi: 10.1128/mcb.11.8.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ibanez C. E., Lipsick J. S. trans activation of gene expression by v-myb. Mol Cell Biol. 1990 May;10(5):2285–2293. doi: 10.1128/mcb.10.5.2285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Introna M., Golay J., Frampton J., Nakano T., Ness S. A., Graf T. Mutations in v-myb alter the differentiation of myelomonocytic cells transformed by the oncogene. Cell. 1990 Dec 21;63(6):1289–1297. doi: 10.1016/0092-8674(90)90424-d. [DOI] [PubMed] [Google Scholar]
  13. Kanter M. R., Smith R. E., Hayward W. S. Rapid induction of B-cell lymphomas: insertional activation of c-myb by avian leukosis virus. J Virol. 1988 Apr;62(4):1423–1432. doi: 10.1128/jvi.62.4.1423-1432.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klempnauer K. H., Bishop J. M. Transduction of c-myb into avian myeloblastosis virus: locating points of recombination within the cellular gene. J Virol. 1983 Dec;48(3):565–572. doi: 10.1128/jvi.48.3.565-572.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klempnauer K. H., Symonds G., Evan G. I., Bishop J. M. Subcellular localization of proteins encoded by oncogenes of avian myeloblastosis virus and avian leukemia virus E26 and by chicken c-myb gene. Cell. 1984 Jun;37(2):537–547. doi: 10.1016/0092-8674(84)90384-2. [DOI] [PubMed] [Google Scholar]
  16. Lane T., Ibanez C., Garcia A., Graf T., Lipsick J. Transformation by v-myb correlates with trans-activation of gene expression. Mol Cell Biol. 1990 Jun;10(6):2591–2598. doi: 10.1128/mcb.10.6.2591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leprince D., Gegonne A., Coll J., de Taisne C., Schneeberger A., Lagrou C., Stehelin D. A putative second cell-derived oncogene of the avian leukaemia retrovirus E26. Nature. 1983 Nov 24;306(5941):395–397. doi: 10.1038/306395a0. [DOI] [PubMed] [Google Scholar]
  18. Moelling K., Pfaff E., Beug H., Beimling P., Bunte T., Schaller H. E., Graf T. DNA-binding activity is associated with purified myb proteins from AMV and E26 viruses and is temperature-sensitive for E26 ts mutants. Cell. 1985 Apr;40(4):983–990. doi: 10.1016/0092-8674(85)90358-7. [DOI] [PubMed] [Google Scholar]
  19. Moscovici C., Samarut J., Gazzolo L., Moscovici M. G. Myeloid and erythroid neoplastic responses to avian defective leukemia viruses in chickens and in quail. Virology. 1981 Sep;113(2):765–768. doi: 10.1016/0042-6822(81)90205-1. [DOI] [PubMed] [Google Scholar]
  20. Moscovici M. G., Jurdic P., Samarut J., Gazzolo L., Mura C. V., Moscovici C. Characterization of the hemopoietic target cells for the avian leukemia virus E26. Virology. 1983 Aug;129(1):65–78. doi: 10.1016/0042-6822(83)90396-3. [DOI] [PubMed] [Google Scholar]
  21. Ness S. A., Marknell A., Graf T. The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell. 1989 Dec 22;59(6):1115–1125. doi: 10.1016/0092-8674(89)90767-8. [DOI] [PubMed] [Google Scholar]
  22. Nunn M. F., Seeburg P. H., Moscovici C., Duesberg P. H. Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature. 1983 Nov 24;306(5941):391–395. doi: 10.1038/306391a0. [DOI] [PubMed] [Google Scholar]
  23. Nunn M., Weiher H., Bullock P., Duesberg P. Avian erythroblastosis virus E26: nucleotide sequence of the tripartite onc gene and of the LTR, and analysis of the cellular prototype of the viral ets sequence. Virology. 1984 Dec;139(2):330–339. doi: 10.1016/0042-6822(84)90378-7. [DOI] [PubMed] [Google Scholar]
  24. Quéva C., Ness S. A., Grässer F. A., Graf T., Vandenbunder B., Stéhelin D. Expression patterns of c-myb and of v-myb induced myeloid-1 (mim-1) gene during the development of the chick embryo. Development. 1992 Jan;114(1):125–133. doi: 10.1242/dev.114.1.125. [DOI] [PubMed] [Google Scholar]
  25. Radke K., Beug H., Kornfeld S., Graf T. Transformation of both erythroid and myeloid cells by E26, an avian leukemia virus that contains the myb gene. Cell. 1982 Dec;31(3 Pt 2):643–653. doi: 10.1016/0092-8674(82)90320-8. [DOI] [PubMed] [Google Scholar]
  26. Ramsay R. G., Ikeda K., Rifkind R. A., Marks P. A. Changes in gene expression associated with induced differentiation of erythroleukemia: protooncogenes, globin genes, and cell division. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6849–6853. doi: 10.1073/pnas.83.18.6849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ramsay R. G., Ishii S., Nishina Y., Soe G., Gonda T. J. Characterization of alternate and truncated forms of murine c-myb proteins. Oncogene Res. 1989;4(4):259–269. [PubMed] [Google Scholar]
  28. 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]
  29. Sakura H., Kanei-Ishii C., Nagase T., Nakagoshi H., Gonda T. J., Ishii S. Delineation of three functional domains of the transcriptional activator encoded by the c-myb protooncogene. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5758–5762. doi: 10.1073/pnas.86.15.5758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shen-Ong G. L., Lüscher B., Eisenman R. N. A second c-myb protein is translated from an alternatively spliced mRNA expressed from normal and 5'-disrupted myb loci. Mol Cell Biol. 1989 Dec;9(12):5456–5463. doi: 10.1128/mcb.9.12.5456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shen-Ong G. L. The myb oncogene. Biochim Biophys Acta. 1990 Jun 1;1032(1):39–52. doi: 10.1016/0304-419x(90)90011-o. [DOI] [PubMed] [Google Scholar]
  32. Thiele C. J., Cohen P. S., Israel M. A. Regulation of c-myb expression in human neuroblastoma cells during retinoic acid-induced differentiation. Mol Cell Biol. 1988 Apr;8(4):1677–1683. doi: 10.1128/mcb.8.4.1677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Walther C., Gruss P. Pax-6, a murine paired box gene, is expressed in the developing CNS. Development. 1991 Dec;113(4):1435–1449. doi: 10.1242/dev.113.4.1435. [DOI] [PubMed] [Google Scholar]
  34. Weston K., Bishop J. M. Transcriptional activation by the v-myb oncogene and its cellular progenitor, c-myb. Cell. 1989 Jul 14;58(1):85–93. doi: 10.1016/0092-8674(89)90405-4. [DOI] [PubMed] [Google Scholar]

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