IKBKB

IKBKB is the gene that encodes the catalytic subunit of the IκB kinase (IKK) complex, known as IKK-β. In humans, IKBKB and its protein product IKK-β are central to the canonical NF-κB signaling pathway. The IKK complex also includes the regulatory subunit NEMO (IKBKG) and the catalytic subunit IKK-α (IKKA). IKK-β is a serine/threonine kinase that, upon activation, phosphorylates IκB proteins such as IκBα, leading to their ubiquitination and proteasomal degradation. This releases NF-κB transcription factors (primarily the p65/p50 dimer) to translocate to the nucleus and regulate immune, inflammatory, and cell-survival genes.

Activation of IKK-β occurs in response to pro-inflammatory stimuli such as TNF-α, IL-1β, LPS, and other signals that converge on the upstream kinase TAK1 (MAP3K7). TAK1 phosphorylation of IKK-β on activation loop serine residues Ser177 and Ser181 promotes full kinase activity. Regulation involves multiple layers, including upstream signals, post-translational modifications, and interactions with the regulatory subunit NEMO.

Clinical and research relevance: dysregulation of the IKK-β/NF-κB pathway is linked to inflammatory diseases and certain cancers. Pharmacological inhibitors targeting IKK-β have been studied for therapeutic potential, though systemic inhibition can lead to immunosuppression and other side effects. IKBKB (IKK-β) is a widely studied component of innate and adaptive immune signaling.