Non-canonical NF-κB signaling pathway

Cell Res. 2011 Jan;21(1):71-85. doi: 10.1038/cr.2010.177. Epub 2010 Dec 21.


The non-canonical NF-κB pathway is an important arm of NF-κB signaling that predominantly targets activation of the p52/RelB NF-κB complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A central signaling component of the non-canonical pathway is NF-κB-inducing kinase (NIK), which integrates signals from a subset of TNF receptor family members and activates a downstream kinase, IκB kinase-α (IKKα), for triggering p100 phosphorylation and processing. A unique mechanism of NIK regulation is through its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction complex and signal-induced non-canonical NF-κB signaling involves NIK stabilization. Tight control of the fate of NIK is important, since deregulated NIK accumulation is associated with lymphoid malignancies.

Publication types

  • Review

MeSH terms

  • Endonucleases
  • Humans
  • I-kappa B Kinase / metabolism
  • NF-kappa B / metabolism*
  • NF-kappa B / physiology
  • Nuclear Proteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction


  • NF-kappa B
  • Nuclear Proteins
  • Protein Serine-Threonine Kinases
  • I-kappa B Kinase
  • NF-kappa B kinase
  • Endonucleases
  • SND1 protein, human