NFkB was originally identified as a factor that binds to the immunoglobulin kappa light chain enhancer in B cells. It was subsequently found in non-B cells in an inactive cytoplasmic form consisting of NFkB bound to IkB. Upon stimulation, IkB is phosphorylated and degraded, and then NF-kB translocates into the nucleus to activate the transcription of target genes. Two IkB proteins, IkBa and IkBb, exhibit divergent biochemical and genetic characteristics, exemplified by their different degradation kinetics. These differences indicate their distinctive physiological functions. Mutated forms of the small G-protein Ras are found in about 30% of all human cancers, including 95% of pancreatic and 50% of colon cancers. KB-RAS is the most commonly mutated form of Ras. KB-RAS was found to interact with the PEST domains of both IkB proteins in vitro. NFkB was originally identified as a heterodimeric DNA binding protein complex consisting of p65 (RelA) and p50 (NFKB1) subunits. Other identified subunits include p52 (NFKB2), c-Rel, and RelB. The p65, cRel, and RelB subunits are responsible for transactivation. The p50 and p52 subunits possess DNA binding activity but limited ability to transactivate. p52 has been reported to form transcriptionally active heterodimers with the NFkB subunit p65, similar to p50/p65 heterodimers. The heterodimers of p52/p65 and p50/p65 are regulated by physical inactivation in the cytoplasm by IkB-a. IkB-a binds to the p65 subunit, preventing nuclear localization and DNA binding. Low levels of p52 and p50 homodimers can also exist in cells.
This affinity purified antibody was prepared from whole rabbit serum produced by repeated immunizations with a synthetic peptide corresponding to aa 179-192 of human KB-RAS. A single amino acid changes of S190P exists in mouse.