The nuclear factor-kappaB, NF-kB/Rel proteins, comprise a family of structurally-related inducible transcription factors which regulate immune and inflammatory responses and apoptosis. These proteins have been linked to numerous diseases, specially cancer, because of the elevated expression of genes encoding antiapoptotic proteins, cytokines, chemokines and cell adhesion molecules. NF-kB family is composed of homo- and heterodimers resulting from the combinatorial association of five polypeptides: p50, p52, p65, cRel and RelB, forming mostly NF-kB1p50/RelAp65 heterodimers. Different combinations of NF-kB/Rel proteins regulate the transcription of different genes and these proteins contain a highly conserved N-terminal DNA-binding/dimerization domain called the Rel Homology Domain (RHD). NF-kB normally resides in the cytoplasm in an inactive form as a complex with IkB kinase, which inhibits NF-kB activity. Phosphorylation of I-kB by IkB kinase (IKK) complex leads to degradation of I-kB and activation of NF-kB allowing NF-kB to translocate to the nucleus and induce target genes.
Ref: Chen, F. Cancer Res. 64, 8135 (2004); Mabuchi, S. et al. J. Biol. Chem. 10, 1074 (2004); Romashkova, JA. and SS. Makarov, Nature 401, 86 (1999); Nolan GP. Cell 64, 961(1991); Lentsch A. Immunol. Ther. Exp. 48, 59 (2000); Hatada EN. et al. Curr. Opin. Immunol. 12, 52 (2000); Magnani M. et al. Curr. Drug Targets 1, 387 (2000); Valen G. et al. J. Am. Coll. Cardio. 38, 307 (2001); May, M. and Ghosh, S. Science 284, 27 (1999). Bonnard M, et al. EMBO J. 19, 4976 (2000); Pomerantz Jl. et al. EMBO J.18, 6694 (1999).