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. 1993 Mar;67(3):1286–1291. doi: 10.1128/jvi.67.3.1286-1291.1993

Structure of a Moloney murine leukemia virus-virus-like 30 recombinant: implications for transduction of the c-Ha-ras proto-oncogene.

A Makris 1, C Patriotis 1, S E Bear 1, P N Tsichlis 1
PMCID: PMC237495  PMID: 8437216

Abstract

Tumor progression locus 2 (Tpl-2) encodes a novel serine-threonine protein kinase which is activated by provirus integration in the late stages of oncogenesis in Moloney leukemia virus (MoMuLV) induced rat T-cell lymphomas. In this report, we present evidence that the provirus integrated in the Tpl-2 locus in 1 of 10 T-cell lymphomas harboring a Tpl-2 rearrangement (2779) is a recombinant between MoMuLV and virus-like 30 (VL30) sequences (Mo-VL30). Recombination between MoMuLV and VL30 may contribute to the transduction of ras, as suggested by the finding that VL30 flanks the ras oncogene in all of the ras transducing viruses isolated from rats to date. The Mo-VL30 recombinant described here represents evidence that recombination between MoMuLV and VL30 can be uncoupled from the transduction of ras, and it may precede the transduction. Sequence comparison between clones of Mo-VL30, Harvey sarcoma virus (Ha-MSV), and genomic c-Ha-ras revealed that all three share a 124-bp region of 87.3% homology. This region was detected at nucleotide positions -1845 to -1720 of c-Ha-ras and 20 bp 5' of the recombination breakpoint between VL30 and ras in Ha-MSV. On the basis of the sequence comparison between VL30, Ha-MSV, and c-Ha-ras, we are proposing a model which explains how VL30 may have facilitated the transduction of c-Ha-ras and perhaps the other ras proto-oncogenes. According to this model, the sequence homology between VL30 and c-Ha-ras targets this gene for transduction by promoting the integration of the provirus in this locus through homologous recombination.

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Selected References

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  1. Chakraborty A. K., Cichutek K., Duesberg P. H. Transforming function of proto-ras genes depends on heterologous promoters and is enhanced by specific point mutations. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2217–2221. doi: 10.1073/pnas.88.6.2217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  3. George D. L., Scott A. F., Trusko S., Glick B., Ford E., Dorney D. J. Structure and expression of amplified cKi-ras gene sequences in Y1 mouse adrenal tumor cells. EMBO J. 1985 May;4(5):1199–1203. doi: 10.1002/j.1460-2075.1985.tb03760.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. HARVEY J. J. AN UNIDENTIFIED VIRUS WHICH CAUSES THE RAPID PRODUCTION OF TUMOURS IN MICE. Nature. 1964 Dec 12;204:1104–1105. doi: 10.1038/2041104b0. [DOI] [PubMed] [Google Scholar]
  5. Hoffman E. K., Trusko S. P., Freeman N., George D. L. Structural and functional characterization of the promoter region of the mouse c-Ki-ras gene. Mol Cell Biol. 1987 Jul;7(7):2592–2596. doi: 10.1128/mcb.7.7.2592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lazo P. A., Klein-Szanto A. J., Tsichlis P. N. T-cell lymphoma lines derived from rat thymomas induced by Moloney murine leukemia virus: phenotypic diversity and its implications. J Virol. 1990 Aug;64(8):3948–3959. doi: 10.1128/jvi.64.8.3948-3959.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Norton J. D., Connor J., Avery R. J. Genesis of Kirsten murine sarcoma virus: sequence analysis reveals recombination points and potential leukaemogenic determinant on parental leukaemia virus genome. Nucleic Acids Res. 1984 Sep 11;12(17):6839–6852. doi: 10.1093/nar/12.17.6839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Rasheed S., Gardner M. B., Huebner R. J. In vitro isolation of stable rat sarcoma viruses. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2972–2976. doi: 10.1073/pnas.75.6.2972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rasheed S., Norman G. L., Heidecker G. Nucleotide sequence of the Rasheed rat sarcoma virus oncogene: new mutations. Science. 1983 Jul 8;221(4606):155–157. doi: 10.1126/science.6344220. [DOI] [PubMed] [Google Scholar]
  10. Tsichlis P. N., Strauss P. G., Lohse M. A. Concerted DNA rearrangements in Moloney murine leukemia virus-induced thymomas: a potential synergistic relationship in oncogenesis. J Virol. 1985 Oct;56(1):258–267. doi: 10.1128/jvi.56.1.258-267.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Tsuchida N., Ryder T., Ohtsubo E. Nucleotide sequence of the oncogene encoding the p21 transforming protein of Kirsten murine sarcoma virus. Science. 1982 Sep 3;217(4563):937–939. doi: 10.1126/science.6287573. [DOI] [PubMed] [Google Scholar]
  12. Velu T. J., Vass W. C., Lowy D. R., Tambourin P. E. Harvey murine sarcoma virus: influences of coding and noncoding sequences on cell transformation in vitro and oncogenicity in vivo. J Virol. 1989 Mar;63(3):1384–1392. doi: 10.1128/jvi.63.3.1384-1392.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wei C. M., Lowy D. R., Scolnick E. M. Mapping of transforming region of the Harvey murine sarcoma virus genome by using insertion-deletion mutants constructed in vitro. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4674–4678. doi: 10.1073/pnas.77.8.4674. [DOI] [PMC free article] [PubMed] [Google Scholar]

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