A complete understanding of DNA-binding proteins that regulate genes in specific tissues promises to reveal important features of such processes as cell differentiation, virus-host cell interactions, and oncogenesis. One of the best known examples of these is the regulatory protein NF-kappa B. This factor is crucial to the expression of the transcriptional enhancer of the Ig kappa gene at the appropriate stage of differentiation in B lymphocytes. It has also been found to be important for activation of the human immunodeficiency virus, the cause of acquired immunodeficiency disease (AIDS), in T lymphocytes. The proposed research is a detailed study of the molecular features of NF-kappa B. We will purify the protein to homogeneity, determine partial amino sequence, and use this to clone its cDNA. Monoclonal and polyclonal antibodies will be prepared from the purified protein and be used to determine the post-translational modification that activates NF-kappa B. Finally, structure-function relationships of the protein will be investigated using in vitro mutagenesis of the cloned cDNA.
