title: AP-1 factors play an important role in transformation induced by the v-rel oncogene.
abstract: v-rel is the oncogenic member of the Rel/NF-kappaB family of transcription factors. The mechanism by which v-Rel induces transformation of avian lymphoid cells and fibroblasts is not precisely known. However, most models propose that v-rel disrupts the normal transcriptional regulatory network. In this study we evaluated the role of AP-1 family members in v-Rel-mediated transformation. The overexpression of v-Rel, c-Rel, and c-Rel delta resulted in a prolonged elevation of c-fos and c-jun expression and in a sustained repression of fra-2 at both the mRNA and protein levels in fibroblasts and lymphoid cells. Moreover, the transforming abilities of these Rel proteins correlated with their ability to alter the expression of these AP-1 factors. v-Rel exhibited the most pronounced effect, whereas c-Rel, with poor transforming ability, elicited only moderate changes in AP-1 levels. Furthermore, c-Rel delta, which exhibits enhanced transforming potential relative to c-Rel, induced intermediate changes in AP-1 expression. To directly evaluate the role of AP-1 family members in the v-Rel transformation process, a supjun-1 transdominant mutant was used. The supjun-1 mutant functions as a general inhibitor of AP-1 activity by inhibiting AP-1-mediated transactivation and by reducing AP-1 DNA-binding activity. Coinfection or sequential infection of fibroblasts or lymphoid cells with viruses carrying rel oncogenes and supjun-1 resulted in a reduction of the transformation efficiency of the Rel proteins. The expression of supjun-1 inhibited the ability of v-Rel transformed lymphoid cells and fibroblasts to form colonies in soft agar by over 70%. Furthermore, the expression of supjun-1 strongly interfered with the ability of v-Rel to morphologically transform avian fibroblasts. This is the first report showing that v-Rel might execute its oncogenic potential through modulating the activity of early response genes.
authors.affiliation: Department of Microbiology and the Institute for Cellular and Molecular Biology, University of Texas at Austin, 78712-1095, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kralova
authors.forename: A S
authors.initials: AS
authors.lastname: Liss
authors.forename: W
authors.initials: W
authors.lastname: Bargmann
authors.forename: H R
authors.initials: HR
authors.lastname: Bose
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D017930:Genes, Reporter; D008957:Models, Genetic; D020572:Oncogene Proteins v-rel; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D013489:Suppression, Genetic; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D020572:Oncogene Proteins v-rel; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D020569:Proto-Oncogene Proteins c-rel; D015682:Retroviridae Proteins, Oncogenic; D018808:Transcription Factor AP-1