NF-κB-inducing kinase (NIK) (NIK)

NF-κB-inducing kinase (NIK), also known as MAP3K14, is a serine/threonine kinase that serves as a central regulator in the non-canonical NF-κB signaling pathway, phosphorylating IKKα to promote processing of p100 to p52 and subsequent nuclear translocation of RelB/p52 dimers for target gene transcription. This pathway controls immune responses, B-cell maturation, cytokine production, and cell survival, distinct from the canonical pathway driven by IKKβ. Excessive NIK activity drives pathological inflammation, autoimmune conditions, and cancers by sustaining non-canonical signaling and enhancing B-cell adhesion or apoptosis resistance. NIK stability is tightly regulated via ubiquitination and proteasomal degradation, with gain-of-function mutants leading to constitutive activation. Its inhibition is explored therapeutically to curb NF-κB hyperactivity, though complete loss impairs intestinal immunity, B-cell maintenance, and lymphoid organ development. Crystal structures confirm NIK adopts an active kinase conformation without phosphorylation, aided by its N-terminal extension.

Other names

NF-κB-inducing kinaseMAP3K14

Kinase inhibition to block non-canonical NF-κB pathway activation