Mutant envelope residues confer a transactivation function onto N-terminalsequences of the v-Rel oncoprotein

The retroviral oncoprotein v-Rel is a member of the Rel/NF-kappa B family o f transcription factors. v-Rel has multiple changes as compared to the prot o-oncoprotein c-Rel, and these changes render v-Rel highly oncogenic in avi an lymphoid cells, Previous results have shown that three mutant residues i n 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, w e show that these mutant Env aa also enable sequences in the N-terminal hal f of v-Rel to activate transcription in yeast and chicken cells, under cond itions where the analogous sequences from c-Rel either do not or only weakl y 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 res tore the transactivation function; other sequences in the N-terminal half o f v-Rel are needed for full transactivating ability, A C terminally-truncat ed form of NF-kappa B p100 (p85), produced in HUT-78 human leukemic cells, also activates transcription in yeast, under conditions where the normal p5 2 and p100 proteins do not. Furthermore, transcriptional activation by p85 in yeast is likely to occur through N-terminal sequences, Taken together, t hese results are consistent with a model in which transactivation by N-term inal Rel Homology (RH) domain sequences in oncogenic Rel family proteins is influenced by sequences outside the RH domain.