Reactome | NIK-->noncanonical NF-kB signaling

NIK-->noncanonical NF-kB signaling

Stable Identifier

R-HSA-5676590

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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In addition to the activation of canonical NF-kB subunits, activation of SYK pathway by Dectin-1 leads to the induction of the non-canonical NF-kB pathway, which mediates the nuclear translocation of RELB-p52 dimers through the successive activation of NF-kB-inducing kinase (NIK) and IkB kinase-alpha (IKKa) (Geijtenbeek & Gringhuis 2009, Gringhuis et al. 2009). Noncanonical activity tends to build more slowly and remain sustained several hours longer than does the activation of canonical NF-kB. The noncanonical NF-kB pathway is characterized by the post-translational processing of NFKB2 (Nuclear factor NF-kappa-B) p100 subunit to the mature p52 subunit. This subsequently leads to nuclear translocation of p52:RELB (Transcription factor RelB) complexes to induce cytokine expression of some genes (C-C motif chemokine 17 (CCL17) and CCL22) and transcriptional repression of others (IL12B) (Gringhuis et al. 2009, Geijtenbeek & Gringhuis 2009, Plato et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
22017430	Non-canonical NF-?B signaling activation and regulation: principles and perspectives Razani, B, Reichardt, AD, Cheng, G	Immunol. Rev.	2011
21173796	Non-canonical NF-kB signaling pathway Sun, SC	Cell Res.	2011
19302050	Regulation and function of NF-kappaB transcription factors in the immune system Karin, M, Vallabhapurapu, S	Annu. Rev. Immunol.	2009
18322009	RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast differentiation Novack, DV, Faccio, R, Sammut, B, Johnson, T, Alhawagri, M, Vaira, S, O'Neal, J, Hirbe, AC, Weilbaecher, KN, Zou, W, Anwisye, I	Proc. Natl. Acad. Sci. U.S.A.	2008