Role of the Rel-family of transcription factors in the regulation of c-myc gene transcription and apoptosis of WEHI 231 murine B-cells.

Abstract

NF-kB elements mediate control of a number of important growth regulatory genes (rev. in Baeuerle, 1991). We have identified two functional NF-kB elements within the murine c-myc gene. The upstream regulatory element or URE is located -1101 to -1091 b.p. upstream of the PI promoter (Duyao et al. 1990). The internal regulatory element or IRE is at +440 to +459 b.p., within exon 1 (Kessler et al. 1992b). Activation of NF-kB by IL-1 in human dermal FS-4 fibroblasts (Kessler et al. 1992a) or by the tax protein of the HTLV-1 virus in T lymphocytes (Duyao et al. 1992) leads to induction of transcription of the c-myc promoter through binding to the URE and IRE. NF-kB is now known to be a family of dimeric transcription factors, whose subunits all contain an amino terminal rei homology domain, which mediates both dimerization and DNA binding. Classical NF-kB is a heterodimer composed of a p50 and a p65 subunit (Ghosh et al. 1990; Ruben et al. 1991). The c-rel gene encodes a 75 kDa protein (Simek and Rice 1988). Various combinations of these Rei family of proteins bind as dimers to NF-kB elements, but their activity has been found to be element specific.