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. 1994 Apr;68(4):2039–2050. doi: 10.1128/jvi.68.4.2039-2050.1994

Evolution of the oncogenic potential of v-rel: rel-induced expression of immunoregulatory receptors correlates with tumor development and in vitro transformation.

J Nehyba 1, R Hrdlicková 1, E H Humphries 1
PMCID: PMC236677  PMID: 8138989

Abstract

v-rel is a viral oncogene that evolved from turkey c-rel, an NF-kappa B-related transcription factor. Numerous structural alterations record the evolutionary selection of v-rel and distinguish it from c-rel. To evaluate the biological significance of these alterations, we constructed a set of five c/v-rel hybrids in which three mutation clusters (c-Rel amino acids 1 to 97,222 to 302, and 328 to 598) were differentially distributed. These constructs, in addition to parental v-rel and c-rel and two C-terminal deletion mutants of c-rel, were expressed from a retroviral vector. An analysis of cells infected with each of the nine viruses revealed that mutations in all three domains contributed to the ability of v-rel to induce two endogenous c-rel target genes, major histocompatibility complex (MHC) class I and class II, in the B-cell line DT95 as well as MHC class II in normal splenocytes. The analysis revealed a strong nonlinear correlation between the ability of a Rel protein to induce expression of MHC proteins and its capacity to produce splenic tumors and establish in vitro transformation. This correlation is consistent with the hypothesis that v-rel transforms by constitutively altering expression of genes regulated by c-rel and in this way simulates events associated with immune response-linked proliferation of cells of hematopoietic origin. Further, the 16 carboxy-terminal amino acids of c-Rel were identified as a domain responsible for producing a cytotoxic and/or cytostatic effect in DT95. Because this effect is likely to differentially influence induction of MHC expression and tumorigenesis/transformation, it may represent one factor that contributes to the nonlinearity of their correlation.

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Selected References

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