Abstract
Avian leukosis virus (ALV)-induced neoplasias are commonly found associated with integrations of proviral DNA in proximity to the myc gene. However, studies suggest that other genetic events are necessary for the complete neoplastic phenotype. A cell line (HP46) derived from an ALV-induced tumor has been analyzed and found to contain, in addition to an alteration in the myc gene, a promoter insertion in the c-rel locus. Both loci expressed large amounts of mRNA coding for their respective proteins. Several rel-related transcripts were expressed in the HP46 line, and four rel-related proteins of lower molecular weight than the wild-type p68c-rel product were detected. At least two of these transcripts contained U5 long terminal repeat sequences on the 5' end of the RNA. Structural data suggest that the messages may have evolved by an alternative splicing mechanism. This is the first example of a promoter insertion in the c-rel locus, a gene whose viral counterpart v-rel is responsible for the induction of lymphoid tumors.
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- Barth C. F., Humphries E. H. Expression of v-rel induces mature B-cell lines that reflect the diversity of avian immunoglobulin heavy- and light-chain rearrangements. Mol Cell Biol. 1988 Dec;8(12):5358–5368. doi: 10.1128/mcb.8.12.5358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beug H., Müller H., Grieser S., Doederlein G., Graf T. Hematopoietic cells transformed in vitro by REVT avian reticuloendotheliosis virus express characteristics of very immature lymphoid cells. Virology. 1981 Dec;115(2):295–309. doi: 10.1016/0042-6822(81)90112-4. [DOI] [PubMed] [Google Scholar]
- Capobianco A. J., Simmons D. L., Gilmore T. D. Cloning and expression of a chicken c-rel cDNA: unlike p59v-rel, p68c-rel is a cytoplasmic protein in chicken embryo fibroblasts. Oncogene. 1990 Mar;5(3):257–265. [PubMed] [Google Scholar]
- Chen C. L., Lehmeyer J. E., Cooper M. D. Evidence for an IgD homologue on chicken lymphocytes. J Immunol. 1982 Dec;129(6):2580–2585. [PubMed] [Google Scholar]
- Chen I. S., Temin H. M. Substitution of 5' helper virus sequences into non-rel portion of reticuloendotheliosis virus strain T suppresses transformation of chicken spleen cells. Cell. 1982 Nov;31(1):111–120. doi: 10.1016/0092-8674(82)90410-x. [DOI] [PubMed] [Google Scholar]
- Chen I. S., Wilhelmsen K. C., Temin H. M. Structure and expression of c-rel, the cellular homolog to the oncogene of reticuloendotheliosis virus strain T. J Virol. 1983 Jan;45(1):104–113. doi: 10.1128/jvi.45.1.104-113.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clurman B. E., Hayward W. S. Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: evidence for stage-specific events. Mol Cell Biol. 1989 Jun;9(6):2657–2664. doi: 10.1128/mcb.9.6.2657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eick D., Bornkamm G. W. Expression of normal and translocated c-myc alleles in Burkitt's lymphoma cells: evidence for different regulation. EMBO J. 1989 Jul;8(7):1965–1972. doi: 10.1002/j.1460-2075.1989.tb03602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enrietto P. J., Payne L. N., Hayman M. J. A recovered avian myelocytomatosis virus that induces lymphomas in chickens: pathogenic properties and their molecular basis. Cell. 1983 Dec;35(2 Pt 1):369–379. doi: 10.1016/0092-8674(83)90170-8. [DOI] [PubMed] [Google Scholar]
- Enrietto P. J., Wyke J. A. The pathogenesis of oncogenic avian retroviruses. Adv Cancer Res. 1983;39:269–314. doi: 10.1016/s0065-230x(08)61037-4. [DOI] [PubMed] [Google Scholar]
- Gélinas C., Temin H. M. The v-rel oncogene encodes a cell-specific transcriptional activator of certain promoters. Oncogene. 1988 Oct;3(4):349–355. [PubMed] [Google Scholar]
- Hannink M., Temin H. M. Transactivation of gene expression by nuclear and cytoplasmic rel proteins. Mol Cell Biol. 1989 Oct;9(10):4323–4336. doi: 10.1128/mcb.9.10.4323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
- Hicks G. G., Mowat M. Integration of Friend murine leukemia virus into both alleles of the p53 oncogene in an erythroleukemic cell line. J Virol. 1988 Dec;62(12):4752–4755. doi: 10.1128/jvi.62.12.4752-4755.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hughes S. H., Greenhouse J. J., Petropoulos C. J., Sutrave P. Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol. 1987 Oct;61(10):3004–3012. doi: 10.1128/jvi.61.10.3004-3012.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamens J., Richardson P., Mosialos G., Brent R., Gilmore T. Oncogenic transformation by vrel requires an amino-terminal activation domain. Mol Cell Biol. 1990 Jun;10(6):2840–2847. doi: 10.1128/mcb.10.6.2840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Moore B. E., Bose H. R., Jr Expression of the c-rel and c-myc proto-oncogenes in avian tissues. Oncogene. 1989 Jul;4(7):845–852. [PubMed] [Google Scholar]
- Morrison L. E., Kabrun N., Mudri S., Hayman M. J., Enrietto P. J. Viral rel and cellular rel associate with cellular proteins in transformed and normal cells. Oncogene. 1989 Jun;4(6):677–683. [PubMed] [Google Scholar]
- Neiman P., Wolf C., Enrietto P. J., Cooper G. M. A retroviral myc gene induces preneoplastic transformation of lymphocytes in a bursal transplantation assay. Proc Natl Acad Sci U S A. 1985 Jan;82(1):222–226. doi: 10.1073/pnas.82.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Payne L. N., Powell P. C., Rennie M. Response of B and T lymphocytes and other blood leukocytes in chickens with Marek's disease. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):817–826. doi: 10.1101/sqb.1974.039.01.095. [DOI] [PubMed] [Google Scholar]
- Peters G., Lee A. E., Dickson C. Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus. Nature. 1986 Apr 17;320(6063):628–631. doi: 10.1038/320628a0. [DOI] [PubMed] [Google Scholar]
- Purchase H. G., Witter R. L. The reticuloendotheliosis viruses. Curr Top Microbiol Immunol. 1975;71:103–124. doi: 10.1007/978-3-642-66193-8_3. [DOI] [PubMed] [Google Scholar]
- Rice N. R., Copeland T. D., Simek S., Oroszlan S., Gilden R. V. Detection and characterization of the protein encoded by the v-rel oncogene. Virology. 1986 Mar;149(2):217–229. doi: 10.1016/0042-6822(86)90123-6. [DOI] [PubMed] [Google Scholar]
- Robinson H. L., Gagnon G. C. Patterns of proviral insertion and deletion in avian leukosis virus-induced lymphomas. J Virol. 1986 Jan;57(1):28–36. doi: 10.1128/jvi.57.1.28-36.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roth S., Stein D., Nüsslein-Volhard C. A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo. Cell. 1989 Dec 22;59(6):1189–1202. doi: 10.1016/0092-8674(89)90774-5. [DOI] [PubMed] [Google Scholar]
- Rushlow C. A., Han K., Manley J. L., Levine M. The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila. Cell. 1989 Dec 22;59(6):1165–1177. doi: 10.1016/0092-8674(89)90772-1. [DOI] [PubMed] [Google Scholar]
- Schwartz R. C., Witte O. N. A recombinant murine retrovirus expressing v-rel is cytopathic. Virology. 1988 Jul;165(1):182–190. doi: 10.1016/0042-6822(88)90671-x. [DOI] [PubMed] [Google Scholar]
- Selten G., Cuypers H. T., Berns A. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas. EMBO J. 1985 Jul;4(7):1793–1798. doi: 10.1002/j.1460-2075.1985.tb03852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simek S., Rice N. R. Detection and characterization of the protein encoded by the chicken c-rel protooncogene. Oncogene Res. 1988;2(2):103–119. [PubMed] [Google Scholar]
- Simek S., Rice N. R. p59v-rel, the transforming protein of reticuloendotheliosis virus, is complexed with at least four other proteins in transformed chicken lymphoid cells. J Virol. 1988 Dec;62(12):4730–4736. doi: 10.1128/jvi.62.12.4730-4736.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Steward R. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science. 1987 Oct 30;238(4827):692–694. doi: 10.1126/science.3118464. [DOI] [PubMed] [Google Scholar]
- Steward R. Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function. Cell. 1989 Dec 22;59(6):1179–1188. doi: 10.1016/0092-8674(89)90773-3. [DOI] [PubMed] [Google Scholar]
- Thompson C. B., Humphries E. H., Carlson L. M., Chen C. L., Neiman P. E. The effect of alterations in myc gene expression on B cell development in the bursa of Fabricius. Cell. 1987 Nov 6;51(3):371–381. doi: 10.1016/0092-8674(87)90633-7. [DOI] [PubMed] [Google Scholar]
- Tung H. Y., Bargmann W. J., Lim M. Y., Bose H. R., Jr The v-rel oncogene product is complexed to a 40-kDa phosphoprotein in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2479–2483. doi: 10.1073/pnas.85.8.2479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walro D. S., Herzog N. K., Zhang J., Lim M. Y., Bose H. R., Jr The transforming protein of avian reticuloendotheliosis virus is a soluble cytoplasmic protein which is associated with a protein kinase activity. Virology. 1987 Oct;160(2):433–444. doi: 10.1016/0042-6822(87)90015-8. [DOI] [PubMed] [Google Scholar]
- Wilhelmsen K. C., Temin H. M. Structure and dimorphism of c-rel (turkey), the cellular homolog to the oncogene of reticuloendotheliosis virus strain T. J Virol. 1984 Feb;49(2):521–529. doi: 10.1128/jvi.49.2.521-529.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]



