Regulation of NF-kappa B and disease control: identification of a novel serine kinase and thioredoxin as effectors for signal transduction pathway for NF-kappa B activation.

We have identified novel signal transduction cascades in activating NF-kappa B, as well as its pathogenetic roles in various disease processes. By applying the basic knowledge obtained through these studies, we hope to find new therapeutic measures against currently incurable diseases such as hematogenic cancer cell metastasis, rheumatoid arthritis, and AIDS. We also propose a novel strategy in screening effective inhibitors against transcription factors. Elucidation of the cis-regulatory element for expression of pathogenetic genes and identification of the responsible transcription factor will not only facilitate the study of pathogenesis but will also promote the development of effective therapy. Recognition of control mechanisms of the NF-kappa B activation pathway has explained the therapeutic efficacy of various compounds with different pharmacologic actions. A similar strategy may be applicable for other inducible transcription factors. From the medical point of view, one of the purposes of these approaches is to find small molecular weight compounds that can be administered orally and that are effective in controlling gene expression of pathogenetic genes.