The NF-kappa B/Rel family of transcription factors in oncogenic transformation and apoptosis

Recent progress in the identification and functional analysis of protein ki nases and adapter molecules that lead to activation of NF-KB family transcr iption factors has lead to a quite detailed understanding of one of the maj or signalling pathways that mediate a cell's response to environmental stre ss in a variety of host-defense situations. NF-kappa B is recognized as a k ey regulatory factor mediating the coordinate expression of genes which are part of the cellular machinery that functions to protect an organism again st damage posed by physical, chemical or microbial noxae. in a wide variety of patho-physiological situations such as immune and inflammatory reaction s, the expression of cytokines, interleukins and adhesion molecules in cell s of the immune system including T and B cells, endothelial as well as phag ocytic/antigen presenting cells is to a large extent regulated by NF-kappa B. Moreover, this transcription factor appears to play a central role in th e regulation of apoptosis, an important cellular program that decides upon a cell's fate not only during embryonic development but also on its way fro m normal to the transformed phenotype. Thus, NF-kappa B has emerged also as an attractive target for therapeutic interference in a variety of patholog ical situations, including chronic inflammatory and autoimmune diseases, HI V infection and cancer. (C) 1999 Elsevier Science B.V. All rights reserved.