Activation of NIK

Stable Identifier
R-HSA-5607721
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Activation of NIK
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The catalytic activity of NF-kB-inducing kinase (NIK) is regulated by structural conformation rather than by phosphorylation events. Under normal conditions NIK may be present in an autoinhibited state in which its constitutively active kinase domain is shielded by the N-terminal inhibitory element and upon receptor induction NIK kinase domain adopts an active conformation, in agreement with its catalytic activity. This catalytically competent conformation is maintained by an N-terminal extension prior to the kinase domain rather than through a phosphorylation event (Liu et al. 2012). NIK, also known as MAP3K14 (MAPK kinase kinase 14), is a serine/threonine kinase in the MAP3K family (Malinin et al. 1997). In unstimulated cells NIK associates with a complex composed of TNF receptor-associated factor 2 (TRAF2), TRAF3 and cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2. This molecular interaction with TRAF-cIAP complex appears to target NIK for ubiquitination and proteasomal degradation. In response to receptor stimulation, TRAF2 or TRAF3, or both are targeted for proteasomal degradation by cIAP-mediated ubiquitination, which triggers the release and stabilization of NIK (Razani et al. 2010).
Literature References
PubMed ID Title Journal Year
20501935 Controlling the fate of NIK: a central stage in noncanonical NF-kappaB signaling

Sun, SC

Sci Signal 2010
22718757 Structure of the nuclear factor ?B-inducing kinase (NIK) kinase domain reveals a constitutively active conformation

Chen, G, Walker, N, Sudom, A, Plotnikova, O, Johnstone, S, Ayres, M, Min, X, Lee, F, Liu, J, Cao, P, Gao, X, Wang, Z, Cao, Z

J. Biol. Chem. 2012
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Orthologous Events
Activation of NIK (Bos taurus)
Activation of NIK (Canis familiaris)
Activation of NIK (Gallus gallus)
Activation of NIK (Mus musculus)
Activation of NIK (Rattus norvegicus)
Activation of NIK (Saccharomyces cerevisiae)
Activation of NIK (Sus scrofa)
Activation of NIK (Xenopus tropicalis)
Authored
Garapati, P V  (2014-07-14)
Reviewed
Geijtenbeek, TB  (2014-09-02)
Created
Garapati, P V  (2014-07-14)
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