Cis Regulatory Control of mos Oncogene Expression

  • Mary Lou McGeady
  • Thomas G. Wood
  • Donald G. Blair
  • Arun Seth
  • Friedrich Propst
  • Marianne Oskarsson
  • Martin Schmidt
  • George Vande Woude
Conference paper
Part of the Veröffentlichungen aus der Geomedizinischen Forschungsstelle der Heidelberger Akademie der Wissenschaften book series (HD AKAD, volume 1987/88 / 1987/4)

Abstract

The viral and cellular homologs of the mos oncogene have been useful for studying the molecular elements required for cell transformation. These studies provided the first direct comparison of a viral oncogene and its cellular counterpart (8,14) and demonstrated that the cellular mos could be activated by viral sequences that cause cell transformation (14). Subsequently, it was shown that the proviral.transcription control element or long terminal repeat (LTR) and its enhancer was responsible for activation of the mouse c-mos (1,2,10,21). The more difficult task of identifying the mechanism by which the mos oncogene causes expression of the transformed phenotype remains to be solved. One approach to this problem has been to study proto-oncogene expression which can reveal important information about possible function. However, because the mos proto-oncogene is expressed at very low levels (15), it escaped detection for many years (5,6,13), and we, therefore, studied the biological activity of LTRactivated c-mos as a means of identifying important regulatory elements within the normal proto-oncogene locus. We first discovered an element called the upstream mouse sequence (UMS) located approximately 1.5 kilo-bases (kb) upstream from c-mosmu. This sequence prevented c-mos activation by a downstream LTR (14,22). UMS was subsequently shown to have both polyadenylation and transcription termination functions (12,22). We identified several regions in mos proto-oncogene loci from three different species, mouse (c-mosmff), human (c-moshu) and chicken (c-mosch) (12,22;Schmidt, in preparation) which reduce biological transforming activity. The c-mosmu sequence has been most extensively characterized.

Keywords

Codon Serine Lysine Sarcoma Thymidine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    BLAIR, D.G.; McCLEMENTS, W.L.;.OSKARSSON, M.K.; FISCHINGER, P.J., and VANDE WOUDE, G.F.: Biological activity of cloned Moloney sarcoma virus DNA: Terminally redundant sequences may enhance transformation efficiency. Proc. Natl. Acad. Sci. USA 77: 3504 - 3508 (1980).PubMedCrossRefGoogle Scholar
  2. 2.
    BLAIR, D.G.; OSKARSSON, M.; WOOD, T.G.; McCLEMENTS, W.L.; FISCHINGER, P.J., and VANDE WOUDE, G.F.: Activation of the transforming potential of a normal cell sequence: A molecular model for oncogenesis. Science 212: 941 - 943 (1981).Google Scholar
  3. 3.
    BLAIR, D.G.; WOOD, T.G.; WOODWORTH, A.M.; McGEADY, M.L.; OSKARSSON, M.K.; PROPST, F.; TAINSKY, M.; COOPER, C.S., WATSON, R.; BAROUDY, B.M., and VANDE WOUDE, G.F.: Properties of the mouse and human mos oncogene loci; in VANDE WOUDE, LEVINE, TOPP, and WATSON, Cancer Cells: Oncogenes and Viral Genes, vol. 2, pp. 281-289 ( Cold Spring Harbor, New York 1984 ).Google Scholar
  4. 4.
    BLAIR, D.G.; OSKARSSON, M.K.; SETH, A.; DUNN, K.J.; DEAN, M.; ZWEIG, M.; TAINSKY, M.A., and VANDE WOUDE, G.F.: Analysis of the transforming potential of the human homolog of mos. Cell 46: 785 - 794 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    GÄTTONI, S.; KIRSCHMEIER, P.; WEINSTEIN, I.B.,; ESCOBEDO, J., and DINA, D.: Cellular Moloney murine sarcoma (c-mos) sequences are hypermethylated and transcriptionally silent in normal and transformed rodent cells. Mol. Cell. Biol. 2: 42 - 51 (1982).PubMedGoogle Scholar
  6. 6.
    GOYETTE, M.; PETROPOULOS, C.J.; SHANK, P.R., and FAUSTO, N.: Regulated transcription of c-Ki-ras and c-myc during compensatory growth of rat liver. Mol. Cell. Biol. 4: 1493 - 1498 (1984).PubMedGoogle Scholar
  7. 7.
    HANNINK, M. and DONOGHUE, D.J.: Lysine residue 121 in the proposed ATP-binding site of the v-mos protein is required for transformation. Proc. Natl. Acad. Sci. USA 82; 7894 - 7898 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    JONES, M.; BOSSELMAN, R.A.; VAN DER HOORN, F.A.; BERNS, A.; FAN, H., and VERMA, I.M.: Identification and molecular cloning of Moloney mouse sarcoma virus-specific sequences from uninfected mouse cells. Proc. Natl. Acad. Sci. USA 77: 2651 - 2655 (1980).PubMedCrossRefGoogle Scholar
  9. 9.
    KLOETZER, W.S.; MAXWELL, S.A., and ARLINGHAUS, R.B.: p85gag-mos encoded by ts110 Moloney murine sarcoma virus has an associated protein kinase activity. Proc. Nati. Acad. Sci. USA 80: 412 - 416 (1983).CrossRefGoogle Scholar
  10. 10.
    LEVINSON, B.; KHOURY, G.; VANDE WOUDE, G., and GRUSS, P.: Activation of the SV40 genome by the 72 base-pair tandem repeats of Moloney sarcoma virus. Nature (London) 295: 568 - 572 (1982).CrossRefGoogle Scholar
  11. 11.
    MAXWELL, S.A. and ARLINGHAUS, R.B.: Serine kinase activity associated with Moloney murine sarcoma virus-124-encoded p37m0S. Virology 143: 321 - 333 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    McGEADY, M.L.; WOOD, T.G.; MAIZEL, J.V., and VANDE WOUDE, G.F.: Sequence upstream to the mouse c-mos oncogene may function as a transcription termination signal. DNA, in press.Google Scholar
  13. 13.
    MULLER, R.; SLAMON, D.J.; TREMBLAY, J.M.; CLINE, M.J., and VERMA, I.M.: Differential expression of cellular oncogenes during pre-and postnatal development of the mouse. Nature 299: 640 - 644 (1982).PubMedCrossRefGoogle Scholar
  14. 14.
    OSKARSSON, M.; McCLEMENTS, W.L.; BLAIR, D.G.; MAIZEL, J.V., and VANDE WOUDE, G.F.: Properties of a normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney murine sarcoma virus. Science 207: 1222 - 1224 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    PROPST, F. and VANDE WOUDE, G.F.: Expression of c-mos proto-oncogene transcripts in mouse tissues. Nature 315: 516 - 518 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    RECHAVI, G.; GIVOL, D., and CANAANI, E.: Activation of a cellular oncogene by DNA rearrangement. Possible involvement of an IS-like element. Nature 300: 607 - 611 (1982).PubMedCrossRefGoogle Scholar
  17. 17.
    SETH, A. and VANDE WOUDE, G.F.: Nucleotide sequence and the biochemical activities of the HT1MSV mos gene. J. Virol. 56: 144 - 152 (1985).PubMedGoogle Scholar
  18. 18.
    VAN BEVEREN, C.; VAN STRAATEN, F.; GALLESHAW, J.A., and VERMA, A.: Nucleotide sequence of the genome of a murine sarcoma virus. Cell 27: 97 - 108 (1981).PubMedCrossRefGoogle Scholar
  19. 19.
    VAN DER HOORN, F.A.; MULLER, V., and PIZER, L.: Sequences upstream of c-mos (rat) that block RNA accumulation in mouse cells do not inhibit in vitro transcription. Mol. Cell. Biol. 5: 406 - 409 (1985).PubMedGoogle Scholar
  20. 20.
    WATSON, R.; OSKARSSON, M., and VANDE WOUDE, G.F.: Human DNA sequence homologous to the transforming gene (mos) of Moloney murine sarcoma virus. Proc. Natl. Acad. Sci. USA 79: 4078 - 4082 (1982).PubMedCrossRefGoogle Scholar
  21. 21.
    WOOD, T.G.; McGEADY, M.L.; BLAIR, D.G., and VANDE WOUDE, G.F.: Long terminal repeat enhancement of v-mos transforming activity: Identification of essential regions. J.Virol. 46: 726 - 736 (1983).PubMedGoogle Scholar
  22. 22.
    WOOD, T.G.; McGEADY, M.L.; BAROUDY, B.M.; BLAIR, D.G., and VANDE WOUDE, G.F.: Mouse c-mos oncogene activation is prevented by upstream sequences. Proc. Natl. Acad. Sci. USA 81: 7817 - 7821 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Mary Lou McGeady
    • 1
  • Thomas G. Wood
    • 1
  • Donald G. Blair
    • 1
  • Arun Seth
    • 1
  • Friedrich Propst
    • 1
  • Marianne Oskarsson
    • 1
  • Martin Schmidt
    • 1
  • George Vande Woude
    • 1
  1. 1.NCI-Frederick Cancer Research FacilityFrederickUSA

Personalised recommendations