Identification of a Naturally Occurring Transforming Variant of the p65 Subunit of NF-κB

Abstract
Transcription factor NF-KB comprises two proteins, p50 and p65, that have sequence similarity to the v-rel oncogene. In primary hematopoietic cell populations an alternatively spliced form of NF-KB p65 mRNA was observed that encoded a protein designated p65Δ. Expression of the p65Δ cDNA in Rat-1 fibroblasts resulted in focus formation, anchorage- independent growth in soft agar, and tumor formation in athymic nude mice, effects not obtained with expression of p65 or a p65Δ mutant that contains a disruption within the transcriptional activation domain. Thus, p65Δ, which associated weakly and interfered with DNA binding by p65, may sequester an essential limiting regulatory factor or factors required for NF-KB function.