NFKB inhibitor alpha (IκBα)

NFKB inhibitor alpha (**IκΒα**) is a key cellular protein that regulates the activity of the transcription factor **NF-kappa B**. It functions primarily by binding to REL dimers such as p65/RelA and p50/NFKB1 subunits, masking their nuclear localization signals, thereby sequestering them in an inactive state within the cytoplasm. This prevents these transcription factors from entering the nucleus and activating genes involved in inflammation, immunity, cell survival, proliferation, and development. Upon receiving appropriate cellular signals—such as those triggered by cytokines or stress—IΚΒa is phosphorylated by specific kinases (IKK complex), leading to its ubiquitination and subsequent proteasomal degradation. This releases active NF-kappa B dimers which then translocate into the nucleus to regulate gene expression. Mutations in NFKBIΑ have been linked with constitutive activation of NF-kappa B signaling observed in some cancers like Hodgkin’s lymphoma. The dynamic regulation between NFKBIΑ mRNA/protein levels plays a critical role during early embryogenesis as well as immune responses[1][3][4].

Other names

IκBαNFKBIANF-kappa-B inhibitor alphaIkappa-B-alphaIKBA protein

Drugs that modulate this pathway typically act by stabilizing IκBα to prevent its degradation (thus inhibiting NF‑κB nuclear translocation), or by inhibiting kinases such as IKK that phosphorylate and mark it for destruction.