Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Apr;85(7):2061–2065. doi: 10.1073/pnas.85.7.2061

The predicted DBL oncogene product defines a distinct class of transforming proteins.

A Eva 1, G Vecchio 1, C D Rao 1, S R Tronick 1, S A Aaronson 1
PMCID: PMC279928  PMID: 3281159

Abstract

The DBL transforming gene was originally identified by transfection of NIH 3T3 cells with DNA from a human B-cell lymphoma. This gene was found to have arisen as a result of recombination of the 3' portion of the DBL protooncogene coding sequences with an unrelated segment of human DNA. It encodes a cytoplasmic protein that is equally distributed between cytosol and crude membrane fractions. To further characterize this transforming gene, a biologically active cDNA clone of the DBL transforming gene mRNA was isolated. Analysis of the sequence of the DBL oncogene cDNA revealed a long open reading frame that encodes a hybrid protein whose first 50 amino acids (at least) derive from a complete exon of a different locus. No significant homology with known oncogenes or any known protein sequences was demonstrated. The computer analysis of the predicted DBL protein indicated it is highly hydrophilic with no hydrophobic domains characteristic of a membrane-spanning region or signal peptide. Thus, the DBL oncoprotein is distinct among known transforming gene products.

Full text

PDF
2061

Selected References

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

  1. Adams S. L., Sobel M. E., Howard B. H., Olden K., Yamada K. M., de Crombrugghe B., Pastan I. Levels of translatable mRNAs for cell surface protein, collagen precursors, and two membrane proteins are altered in Rous sarcoma virus-transformed chick embryo fibroblasts. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3399–3403. doi: 10.1073/pnas.74.8.3399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beck T. W., Huleihel M., Gunnell M., Bonner T. I., Rapp U. R. The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus. Nucleic Acids Res. 1987 Jan 26;15(2):595–609. doi: 10.1093/nar/15.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berg J. M. Potential metal-binding domains in nucleic acid binding proteins. Science. 1986 Apr 25;232(4749):485–487. doi: 10.1126/science.2421409. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  6. Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
  7. Cooper C. S., Park M., Blair D. G., Tainsky M. A., Huebner K., Croce C. M., Vande Woude G. F. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature. 1984 Sep 6;311(5981):29–33. doi: 10.1038/311029a0. [DOI] [PubMed] [Google Scholar]
  8. Corden J., Wasylyk B., Buchwalder A., Sassone-Corsi P., Kedinger C., Chambon P. Promoter sequences of eukaryotic protein-coding genes. Science. 1980 Sep 19;209(4463):1406–1414. doi: 10.1126/science.6251548. [DOI] [PubMed] [Google Scholar]
  9. Di Fiore P. P., Pierce J. H., Kraus M. H., Segatto O., King C. R., Aaronson S. A. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178–182. doi: 10.1126/science.2885917. [DOI] [PubMed] [Google Scholar]
  10. Dush M. K., Sikela J. M., Khan S. A., Tischfield J. A., Stambrook P. J. Nucleotide sequence and organization of the mouse adenine phosphoribosyltransferase gene: presence of a coding region common to animal and bacterial phosphoribosyltransferases that has a variable intron/exon arrangement. Proc Natl Acad Sci U S A. 1985 May;82(9):2731–2735. doi: 10.1073/pnas.82.9.2731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dynan W. S., Sazer S., Tjian R., Schimke R. T. Transcription factor Sp1 recognizes a DNA sequence in the mouse dihydrofolate reductase promoter. Nature. 1986 Jan 16;319(6050):246–248. doi: 10.1038/319246a0. [DOI] [PubMed] [Google Scholar]
  12. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  13. Eva A., Aaronson S. A. Isolation of a new human oncogene from a diffuse B-cell lymphoma. Nature. 1985 Jul 18;316(6025):273–275. doi: 10.1038/316273a0. [DOI] [PubMed] [Google Scholar]
  14. Eva A., Vecchio G., Diamond M., Tronick S. R., Ron D., Cooper G. M., Aaronson S. A. Independently activated dbl oncogenes exhibit similar yet distinct structural alterations. Oncogene. 1987;1(4):355–360. [PubMed] [Google Scholar]
  15. Fasano O., Birnbaum D., Edlund L., Fogh J., Wigler M. New human transforming genes detected by a tumorigenicity assay. Mol Cell Biol. 1984 Sep;4(9):1695–1705. doi: 10.1128/mcb.4.9.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fitzgerald M., Shenk T. The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs. Cell. 1981 Apr;24(1):251–260. doi: 10.1016/0092-8674(81)90521-3. [DOI] [PubMed] [Google Scholar]
  17. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  18. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  19. Hall A., Brown R. Human N-ras: cDNA cloning and gene structure. Nucleic Acids Res. 1985 Jul 25;13(14):5255–5268. doi: 10.1093/nar/13.14.5255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ingolia D. E., Al-Ubaidi M. R., Yeung C. Y., Bigo H. A., Wright D., Kellems R. E. Molecular cloning of the murine adenosine deaminase gene from a genetically enriched source: identification and characterization of the promoter region. Mol Cell Biol. 1986 Dec;6(12):4458–4466. doi: 10.1128/mcb.6.12.4458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ishii S., Merlino G. T., Pastan I. Promoter region of the human Harvey ras proto-oncogene: similarity to the EGF receptor proto-oncogene promoter. Science. 1985 Dec 20;230(4732):1378–1381. doi: 10.1126/science.2999983. [DOI] [PubMed] [Google Scholar]
  23. Ishii S., Xu Y. H., Stratton R. H., Roe B. A., Merlino G. T., Pastan I. Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4920–4924. doi: 10.1073/pnas.82.15.4920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  26. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  27. Martin-Zanca D., Hughes S. H., Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. 1986 Feb 27-Mar 5Nature. 319(6056):743–748. doi: 10.1038/319743a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. McGrath J. P., Capon D. J., Smith D. H., Chen E. Y., Seeburg P. H., Goeddel D. V., Levinson A. D. Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature. 1983 Aug 11;304(5926):501–506. doi: 10.1038/304501a0. [DOI] [PubMed] [Google Scholar]
  30. Melton D. W., Konecki D. S., Brennand J., Caskey C. T. Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2147–2151. doi: 10.1073/pnas.81.7.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Park M., Dean M., Cooper C. S., Schmidt M., O'Brien S. J., Blair D. G., Vande Woude G. F. Mechanism of met oncogene activation. Cell. 1986 Jun 20;45(6):895–904. doi: 10.1016/0092-8674(86)90564-7. [DOI] [PubMed] [Google Scholar]
  33. Perlman D., Halvorson H. O. A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides. J Mol Biol. 1983 Jun 25;167(2):391–409. doi: 10.1016/s0022-2836(83)80341-6. [DOI] [PubMed] [Google Scholar]
  34. Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275–285. doi: 10.1016/0092-8674(84)90549-x. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Shapiro M. B., Senapathy P. Automated preparation of DNA sequences for publication. Nucleic Acids Res. 1986 Jan 10;14(1):65–73. doi: 10.1093/nar/14.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Srivastava S. K., Wheelock R. H., Aaronson S. A., Eva A. Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8868–8872. doi: 10.1073/pnas.83.23.8868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stanton V. P., Jr, Cooper G. M. Activation of human raf transforming genes by deletion of normal amino-terminal coding sequences. Mol Cell Biol. 1987 Mar;7(3):1171–1179. doi: 10.1128/mcb.7.3.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Taira M., Yoshida T., Miyagawa K., Sakamoto H., Terada M., Sugimura T. cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity. Proc Natl Acad Sci U S A. 1987 May;84(9):2980–2984. doi: 10.1073/pnas.84.9.2980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Takahashi M., Cooper G. M. ret transforming gene encodes a fusion protein homologous to tyrosine kinases. Mol Cell Biol. 1987 Apr;7(4):1378–1385. doi: 10.1128/mcb.7.4.1378. [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. Weinberg R. A. Fewer and fewer oncogenes. Cell. 1982 Aug;30(1):3–4. doi: 10.1016/0092-8674(82)90003-4. [DOI] [PubMed] [Google Scholar]
  43. Winberg G., Hammarskjöld M. L. Isolation of DNA from agarose gels using DEAE-paper. Application to restriction site mapping of adenovirus type 16 DNA. Nucleic Acids Res. 1980 Jan 25;8(2):253–264. doi: 10.1093/nar/8.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yang J. K., Masters J. N., Attardi G. Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes. J Mol Biol. 1984 Jun 25;176(2):169–187. doi: 10.1016/0022-2836(84)90419-4. [DOI] [PubMed] [Google Scholar]
  45. Young D., Waitches G., Birchmeier C., Fasano O., Wigler M. Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell. 1986 Jun 6;45(5):711–719. doi: 10.1016/0092-8674(86)90785-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES