Nuclear factor kappa-B p105 subunit (NFKB1 (p105))

Nuclear factor kappa-B p105 subunit is a large precursor protein encoded by the NFKB1 gene in humans. It functions both as a cytoplasmic inhibitor—retaining other NF-kappa-B proteins—and as a source for generating the active DNA-binding subunit known as p50 via cotranslational processing by the proteasome. The mature forms participate in homo-/heterodimeric transcription factors that regulate over 200 genes involved in immunity, inflammation, cell growth/proliferation, differentiation, apoptosis, and tumorigenesis. Dysregulation is implicated in various diseases including cancer and chronic inflammatory conditions. The canonical complex most often involves heterodimers with RELA/p65 or RELB partners binding κB sites within target gene promoters/enhancers.

Other names

DNA-binding factor KBF1EBP-1Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1NF-kappa-B p105 subunitNFKB1 (gene symbol)

Drugs targeting this molecule or its pathway generally act by inhibiting proteasome-mediated degradation of IκB proteins, thereby preventing activation and nuclear translocation of active NF-kappa-B complexes. Some agents inhibit upstream kinases such as IKKs to block signal-induced activation. The effect on p105 is typically through altered processing to the active p50 form.