THE V-REL ONCOPROTEIN INCREASES EXPRESSION FROM SP1 SITE-CONTAINING PROMOTERS IN CHICKEN-EMBRYO FIBROBLASTS

The v-Rel oncoprotein of the avian Rev-T retrovirus is a member of a f amily of related transcription factors, which also includes the subuni ts of NF-kappaB and several other interacting cellular proteins. We sh ow here that v-Rel specifically increased expression from a reporter p lasmid containing multiple Spl binding sites approximately sixfold in chicken embryo fibroblasts (CEFs), even though v-Rel did not bind dire ctly to these sites. v-Rel also increased expression from a reporter p lasmid containing a human immunodeficiency virus type 1 (HIV-1) long t erminal repeat (LTR) in which the kappaB binding sites were mutated bu t which still contained intact Sp1 binding sites. The increase in Sp1- site transactivation does not precisely correlate with transformation by v-Rel since one non-transforming v-Rel mutant still induced express ion from the Sp1 site-containing promoter. v-Rel appears to increase e xpression from Sp1 site-containing promoters by affecting the transact ivation domain of Sp1, since v-Rel increased the activity of a Gal4-Sp 1 fusion protein, which contains the Spl transactivation domain but la cks the Sp1 DNA-binding domain. As compared with v-Rel, c-Rel induced only a slight increase in expression from the reporter plasmid contain ing Sp1 sites. However, v-Ras and v-Src (but not v-Myb) induced increa ses in transcription from the reporter plasmid containing Sp1 sites to the same extent as v-Rel, but through pathways that appear to be inde pendent from v-Rel. These results suggest that certain oncoproteins mi ght increase transcription from many genes that contain Sp1 binding si tes, and that this might be important for certain aspects of transform ation by these proteins.