Upstream signal transduction of NF-kappaB activation.

NF-kappaB is a transcription factor governing the expression of genes involved in the immune response, embryo or cell lineage development, cell apoptosis, cell cycle progression, inflammation, and oncogenesis. During the past few years, considerable attention has been paid to the upstream signaling pathways that lead to the activation of NF-kappaB. Many of these signaling molecules can serve as potential pharmaceutical targets for the specific inhibition of NF-kappaB activation leading to interruption of disease processes. How these molecules interact with each other is however, still a debatable issue. Since many of the signal molecules in this pathway relay more than one of the upstream signals to downstream targets, it has been suggested that the transmission of signals involves a network, rather than a linear sequence in the activation of NF-kappaB. Thus, the detailed elucidation of the upstream signaling molecules involved with NF-kappaB activation will be important to the development of pharmaceutical inhibitors that specifically inhibit the activation of NF-kappaB. Such inhibitors would be predicted to have potent anti-inflammatory and/or anti-carcinogenic effects.