TRANSFORMATION OF AVIAN FIBROBLASTS OVEREXPRESSING THE C-REL PROTOONCOGENE AND A VARIANT OF C-REL LACKING 40 C-TERMINAL AMINO-ACIDS

The v-rel oncogene was derived from the c-rel proto-oncogene, which en codes a transcriptional activator. Expression of v-rel transforms avia n hematopoietic cells and fibroblasts. Here we report that overexpress ion (via a replication-competent retroviral vector) of full-length c-R el as well as a 40-amino-acid, carboxy-terminal deletion construct of c-Rel (c-Rel Delta) resulted in the morphological transformation of ch icken embryo fibroblasts (CEFs). Subcellular localization of Rel polyp eptides in these transformed cells as determined by immunofluorescence and immunoprecipitation revealed their presence in both the nucleus a nd the cytoplasm, with the majority of Rel polypeptides showing cytopl asmic localization. Cytoplasmic localization could be due to interacti on with I kappa B molecules, and in fact, the overexpression of c-Rel or the C-terminal deletion construct of c-Rel resulted in an increase in the levels of mRNA encoding the avian I kappa B protein pp40 and th e avian homolog of the NF-kappa B protein, p105. However, expression o f v-Rel resulted in the induction of pp40 mRNA only. While c-Rel was a weak activator of kappa B-mediated transcription of a reporter constr uct in transformed CEFs, v-Rel and c-Rel Delta were transcriptional re pressors. However, in spite of these differences, all of these protein s resulted in the transformation of CEFs.