Envelope-dependent transactivation by the retroviral oncoprotein v-Rel is required for efficient malignant transformation of chicken spleen cells.
The retroviral oncoprotein v-Rel is a chimeric protein that has 11 helper virus-derived Envelope (Env) amino acids (aa) at its N terminus. Within these N-terminal Env aa of v-Rel there are three aa substitutions compared to the Rev-A helper virus Env. These aa substitutions have previously been shown to impart a number of unique properties onto v-Rel, including increased transforming and transactivating ability. In this study, we have analysed the sequence requirements for the Env aa to influence several properties of v-Rel. Phe residues at aa 3 and 9 are critical for an N-terminal transactivation function of v-Rel, and the analysis of several Env mutants demonstrates that transactivation ability parallels the transforming ability of v-Rel. Substitutions of conservative aa, such as leucine and tyrosine, for Phe 3 and 9 are tolerated for transactivation in chicken embryo fibroblasts and for transformation of chicken spleen cells. In contrast, the substitution of 10 Phe residues at the N terminus of v-Rel does not enable transactivation, indicating that a distinct structure surrounding Phe-3 and Phe-9 is essential for v-Rel function. We also show that the addition of the v-Rel Env aa to the N terminus of human c-Rel can enable it to activate transcription. Taken together, these results indicate that Phe residues at positions 3 and 9 have been selected for their ability to enhance the oncogenicity of v-Rel by increasing its ability to activate transcription.
Epinat
J C
JC
Department of Biology, Boston University, Massachusetts 02215-2406, USA.
Dvorin
E L
EL
Gilmore
T D
TD
D019943:Amino Acid Substitution; D000596:Amino Acids; D000818:Animals; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002645:Chickens; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism; D020572:Oncogene Proteins v-rel / Q000235:genetics / Q000378:metabolism*; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D012441:Saccharomyces cerevisiae; D013154:Spleen / Q000166:cytology; D015533:Transcriptional Activation
D000596:Amino Acids; D015686:Gene Products, env; D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D010649:Phenylalanine; D004247:DNA