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. 1984 Jun;3(6):1333–1338. doi: 10.1002/j.1460-2075.1984.tb01972.x

The second oncogene mil of avian retrovirus MH2 is related to the src gene family.

F Galibert, S Dupont de Dinechin, M Righi, D Stehelin
PMCID: PMC557518  PMID: 6086317

Abstract

The nucleotide sequence of a PstI fragment prepared from a cloned MH2 virus genome, pMH2-Hd, has been deduced using chemical and enzymatic methods. This fragment, 1862 nucleotides in length, starts with the gag gene, encodes the v-mil sequence and stops within the v-myc gene. This sequence shows that the v-mil gene is fused to the gag gene giving rise to a fused polyprotein of 98 000 daltons: 515 amino acids at the amino terminus would correspond to p10, p19, p27 and part of p12 determinants, 347 amino acids at the carboxy terminus correspond to the v-mil specific sequence. The mil protein shares homology with a number of onc proteins such as src, fes, fms, mos, yes, fps and erbB, as well as with the catalytic chain of the cAMP-dependent protein kinase. This PstI fragment also encodes the beginning of the myc gene which was integrated in MH2 along with the 3' end of the preceding intron placing an acceptor splice site in front of the used open reading frame. As deduced from the sequence, the MH2 myc protein is not identical to the MC29 myc protein. It differs at its amino terminus, which contains little or no gag determinants, depending on the ATG used to initiate translation.

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Selected References

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  1. Alexander R. W., Moscovici C., Vogt P. K. Avian oncovirus Mill Hill No. 2: pathogenicity in chickens. J Natl Cancer Inst. 1979 Feb;62(2):359–366. [PubMed] [Google Scholar]
  2. Alitalo K., Bishop J. M., Smith D. H., Chen E. Y., Colby W. W., Levinson A. D. Nucleotide sequence to the v-myc oncogene of avian retrovirus MC29. Proc Natl Acad Sci U S A. 1983 Jan;80(1):100–104. doi: 10.1073/pnas.80.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barker W. C., Dayhoff M. O. Viral src gene products are related to the catalytic chain of mammalian cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1982 May;79(9):2836–2839. doi: 10.1073/pnas.79.9.2836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonner T., O'Brien S. J., Nash W. G., Rapp U. R., Morton C. C., Leder P. The human homologs of the raf (mil) oncogene are located on human chromosomes 3 and 4. Science. 1984 Jan 6;223(4631):71–74. doi: 10.1126/science.6691137. [DOI] [PubMed] [Google Scholar]
  5. Bryant D., Parsons J. T. Site-directed point mutation in the src gene oF rous sarcoma virus results in an inactive src gene product. J Virol. 1983 Mar;45(3):1211–1216. doi: 10.1128/jvi.45.3.1211-1216.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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(7):1087–1092. doi: 10.1002/j.1460-2075.1983.tb01550.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cairns J. The origin of human cancers. Nature. 1981 Jan 29;289(5796):353–357. doi: 10.1038/289353a0. [DOI] [PubMed] [Google Scholar]
  8. Capon D. J., Chen E. Y., Levinson A. D., Seeburg P. H., Goeddel D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33–37. doi: 10.1038/302033a0. [DOI] [PubMed] [Google Scholar]
  9. Claverie J. M. A common philosophy and FORTRAN 77 software package for implementing and searching sequence databases. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):397–407. doi: 10.1093/nar/12.1part1.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coll J., Righi M., Taisne C., Dissous C., Gegonne A., Stehelin D. Molecular cloning of the avian acute transforming retrovirus MH2 reveals a novel cell-derived sequence (v-mil) in addition to the myc oncogene. EMBO J. 1983;2(12):2189–2194. doi: 10.1002/j.1460-2075.1983.tb01722.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crawford B. D., Barrett J. C., Ts'o P. O. Neoplastic conversion of preneoplastic Syrian hamster cells: rate estimation by fluctuation analysis. Mol Cell Biol. 1983 May;3(5):931–945. doi: 10.1128/mcb.3.5.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Diamond A., Cooper G. M., Ritz J., Lane M. A. Identification and molecular cloning of the human Blym transforming gene activated in Burkitt's lymphomas. Nature. 1983 Sep 8;305(5930):112–116. doi: 10.1038/305112a0. [DOI] [PubMed] [Google Scholar]
  13. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  14. Goubin G., Goldman D. S., Luce J., Neiman P. E., Cooper G. M. Molecular cloning and nucleotide sequence of a transforming gene detected by transfection of chicken B-cell lymphoma DNA. Nature. 1983 Mar 10;302(5904):114–119. doi: 10.1038/302114a0. [DOI] [PubMed] [Google Scholar]
  15. Graf T., Stéhelin D. Avian leukemia viruses. Oncogenes and genome structure. Biochim Biophys Acta. 1982 Jun 28;651(4):245–271. doi: 10.1016/0304-419x(82)90014-2. [DOI] [PubMed] [Google Scholar]
  16. Hampe A., Gobet M., Sherr C. J., Galibert F. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci U S A. 1984 Jan;81(1):85–89. doi: 10.1073/pnas.81.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hampe A., Laprevotte I., Galibert F., Fedele L. A., Sherr C. J. Nucleotide sequences of feline retroviral oncogenes (v-fes) provide evidence for a family of tyrosine-specific protein kinase genes. Cell. 1982 Oct;30(3):775–785. doi: 10.1016/0092-8674(82)90282-3. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Hayashi K. A cloning vehicle suitable for strand separation. Gene. 1980 Oct;11(1-2):109–115. doi: 10.1016/0378-1119(80)90091-8. [DOI] [PubMed] [Google Scholar]
  20. Hayman M. J., Kitchener G., Graf T. Cells transformed by avian myelocytomatosis virus strain CMII contain a 90K gag-related protein. Virology. 1979 Oct 15;98(1):191–199. doi: 10.1016/0042-6822(79)90537-3. [DOI] [PubMed] [Google Scholar]
  21. Hayman M. J., Ramsay G. M., Savin K., Kitchener G., Graf T., Beug H. Identification and characterization of the avian erythroblastosis virus erbB gene product as a membrane glycoprotein. Cell. 1983 Feb;32(2):579–588. doi: 10.1016/0092-8674(83)90477-4. [DOI] [PubMed] [Google Scholar]
  22. Hu S. S., Moscovici C., Vogt P. K. The defectiveness of Mill Hill 2, a carcinoma-inducing avian oncovirus. Virology. 1978 Aug;89(1):162–178. doi: 10.1016/0042-6822(78)90049-1. [DOI] [PubMed] [Google Scholar]
  23. Hérissé J., Courtois G., Galibert F. Nucleotide sequence of the EcoRI D fragment of adenovirus 2 genome. Nucleic Acids Res. 1980 May 24;8(10):2173–2192. doi: 10.1093/nar/8.10.2173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ish-Horowicz D., Burke J. F. Rapid and efficient cosmid cloning. Nucleic Acids Res. 1981 Jul 10;9(13):2989–2998. doi: 10.1093/nar/9.13.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jansen H. W., Lurz R., Bister K., Bonner T. I., Mark G. E., Rapp U. R. Homologous cell-derived oncogenes in avian carcinoma virus MH2 and murine sarcoma virus 3611. Nature. 1984 Jan 19;307(5948):281–284. doi: 10.1038/307281a0. [DOI] [PubMed] [Google Scholar]
  26. Jansen H. W., Patschinsky T., Bister K. Avian oncovirus MH2: molecular cloning of proviral DNA and structural analysis of viral RNA and protein. J Virol. 1983 Oct;48(1):61–73. doi: 10.1128/jvi.48.1.61-73.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jansen H. W., Rückert B., Lurz R., Bister K. Two unrelated cell-derived sequences in the genome of avian leukemia and carcinoma inducing retrovirus MH2. EMBO J. 1983;2(11):1969–1975. doi: 10.1002/j.1460-2075.1983.tb01686.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kan N. C., Flordellis C. S., Garon C. F., Duesberg P. H., Papas T. S. Avian carcinoma virus MH2 contains a transformation-specific sequence, mht, and shares the myc sequence with MC29, CMII, and OK10 viruses. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6566–6570. doi: 10.1073/pnas.80.21.6566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kitamura N., Kitamura A., Toyoshima K., Hirayama Y., Yoshida M. Avian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus. Nature. 1982 May 20;297(5863):205–208. doi: 10.1038/297205a0. [DOI] [PubMed] [Google Scholar]
  30. Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
  31. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Linial M. Two retroviruses with similar transforming genes exhibit differences in transforming potential. Virology. 1982 Jun;119(2):382–391. doi: 10.1016/0042-6822(82)90097-6. [DOI] [PubMed] [Google Scholar]
  34. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  35. Miller A. D., Verma I. M. Two base changes restore infectivity to a noninfectious molecular clone of Moloney murine leukemia virus (pMLV-1). J Virol. 1984 Jan;49(1):214–222. doi: 10.1128/jvi.49.1.214-222.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Murray M. J., Cunningham J. M., Parada L. F., Dautry F., Lebowitz P., Weinberg R. A. The HL-60 transforming sequence: a ras oncogene coexisting with altered myc genes in hematopoietic tumors. Cell. 1983 Jul;33(3):749–757. doi: 10.1016/0092-8674(83)90017-x. [DOI] [PubMed] [Google Scholar]
  37. Neel B. G., Jhanwar S. C., Chaganti R. S., Hayward W. S. Two human c-onc genes are located on the long arm of chromosome 8. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7842–7846. doi: 10.1073/pnas.79.24.7842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pachl C., Biegalke B., Linial M. RNA and protein encoded by MH2 virus: evidence for subgenomic expression of v-myc. J Virol. 1983 Jan;45(1):133–139. doi: 10.1128/jvi.45.1.133-139.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rapp U. R., Reynolds F. H., Jr, Stephenson J. R. New mammalian transforming retrovirus: demonstration of a polyprotein gene product. J Virol. 1983 Mar;45(3):914–924. doi: 10.1128/jvi.45.3.914-924.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rothman J. E., Katz F. N., Lodish H. F. Glycosylation of a membrane protein is restricted to the growing polypeptide chain but is not necessary for insertion as a transmembrane protein. Cell. 1978 Dec;15(4):1447–1454. doi: 10.1016/0092-8674(78)90068-5. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  43. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Saule S., Coll J., Righi M., Lagrou C., Raes M. B., Stehelin D. Two different types of transcription for the myelocytomatosis viruses MH2 and CMII. EMBO J. 1983;2(6):805–809. doi: 10.1002/j.1460-2075.1983.tb01506.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schwartz D. E., Tizard R., Gilbert W. Nucleotide sequence of Rous sarcoma virus. Cell. 1983 Mar;32(3):853–869. doi: 10.1016/0092-8674(83)90071-5. [DOI] [PubMed] [Google Scholar]
  46. Segrest J. P., Feldmann R. J. Membrane proteins: amino acid sequence and membrane penetration. J Mol Biol. 1974 Aug 25;87(4):853–858. doi: 10.1016/0022-2836(74)90090-4. [DOI] [PubMed] [Google Scholar]
  47. Shibuya M., Hanafusa H. Nucleotide sequence of Fujinami sarcoma virus: evolutionary relationship of its transforming gene with transforming genes of other sarcoma viruses. Cell. 1982 Oct;30(3):787–795. doi: 10.1016/0092-8674(82)90283-5. [DOI] [PubMed] [Google Scholar]
  48. Shimizu K., Birnbaum D., Ruley M. A., Fasano O., Suard Y., Edlund L., Taparowsky E., Goldfarb M., Wigler M. Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1. Nature. 1983 Aug 11;304(5926):497–500. doi: 10.1038/304497a0. [DOI] [PubMed] [Google Scholar]
  49. Stephens R. M., Rice N. R., Hiebsch R. R., Bose H. R., Jr, Gilden R. V. Nucleotide sequence of v-rel: the oncogene of reticuloendotheliosis virus. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6229–6233. doi: 10.1073/pnas.80.20.6229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Struck D. K., Lennarz W. J., Brew K. Primary structural requirements for the enzymatic formation of the N-glycosidic bond in glycoproteins. Studies with alpha-lactalbumin. J Biol Chem. 1978 Aug 25;253(16):5786–5794. [PubMed] [Google Scholar]
  51. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  52. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Van Beveren C., van Straaten F., Galleshaw J. A., Verma I. M. Nucleotide sequence of the genome of a murine sarcoma virus. Cell. 1981 Nov;27(1 Pt 2):97–108. doi: 10.1016/0092-8674(81)90364-0. [DOI] [PubMed] [Google Scholar]
  54. Vennström B., Bishop J. M. Isolation and characterization of chicken DNA homologous to the two putative oncogenes of avian erythroblastosis virus. Cell. 1982 Jan;28(1):135–143. doi: 10.1016/0092-8674(82)90383-x. [DOI] [PubMed] [Google Scholar]
  55. Yamamoto T., Nishida T., Miyajima N., Kawai S., Ooi T., Toyoshima K. The erbB gene of avian erythroblastosis virus is a member of the src gene family. Cell. 1983 Nov;35(1):71–78. doi: 10.1016/0092-8674(83)90209-x. [DOI] [PubMed] [Google Scholar]
  56. Yuasa Y., Srivastava S. K., Dunn C. Y., Rhim J. S., Reddy E. P., Aaronson S. A. Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene. Nature. 1983 Jun 30;303(5920):775–779. doi: 10.1038/303775a0. [DOI] [PubMed] [Google Scholar]
  57. ar-Rushdi A., Nishikura K., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983 Oct 28;222(4622):390–393. doi: 10.1126/science.6414084. [DOI] [PubMed] [Google Scholar]

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