title: Mutant envelope residues confer a transactivation function onto N-terminal sequences of the v-Rel oncoprotein.
abstract: The retroviral oncoprotein v-Rel is a member of the Rel/ NF-kappaB family of transcription factors. v-Rel has multiple changes as compared to the proto-oncoprotein c-Rel, and these changes render v-Rel highly oncogenic in avian lymphoid cells. Previous results have shown that three mutant residues in the eleven helper virus-derived Envelope (Env) amino acids (aa) at the N-terminus of v-Rel are required for its full oncogenicity. In this report, we show that these mutant Env aa also enable sequences in the N-terminal half of v-Rel to activate transcription in yeast and chicken cells, under conditions where the analogous sequences from c-Rel either do not or only weakly activate transcription. Removal of the Env aa from v-Rel or site-directed mutations that revert the three mutant residues to the residues present in the Rev-A helper virus Env protein abolish this transactivation ability of v-Rel. Addition of mutant Env aa onto c-Rel is not sufficient to fully restore the transactivation function; other sequences in the N-terminal half of v-Rel are needed for full transactivating ability. A C terminally-truncated form of NF-kappaB p100 (p85), produced in HUT-78 human leukemic cells, also activates transcription in yeast, under conditions where the normal p52 and p100 proteins do not. Furthermore, transcriptional activation by p85 in yeast is likely to occur through N-terminal sequences. Taken together, these results are consistent with a model in which transactivation by N-terminal Rel Homology (RH) domain sequences in oncogenic Rel family proteins is influenced by sequences outside the RH domain.
authors.affiliation: Department of Biology, Boston University, Massachusetts 02215-2406, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Epinat
authors.forename: D
authors.initials: D
authors.lastname: Kazandjian
authors.forename: D D
authors.initials: DD
authors.lastname: Harkness
authors.forename: S
authors.initials: S
authors.lastname: Petros
authors.forename: J
authors.initials: J
authors.lastname: Dave
authors.forename: D W
authors.initials: DW
authors.lastname: White
authors.forename: T D
authors.initials: TD
authors.lastname: Gilmore
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052003:NF-kappa B p52 Subunit; D020572:Oncogene Proteins v-rel / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D015686:Gene Products, env; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D020572:Oncogene Proteins v-rel; D010446:Peptide Fragments; D020569:Proto-Oncogene Proteins c-rel; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors