Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated?
The IkappaB kinases (IKKs) IKK-alpha and IKK-beta, and the IKK-related kinases TBK1 and IKK-epsilon, have essential roles in innate immunity through signal-induced activation of NF-kappaB, IRF3 and IRF7, respectively. Although the signaling events within these pathways have been extensively studied, the mechanisms of IKK and IKK-related complex assembly and activation remain poorly defined. Recent data provide insight into the requirement for scaffold proteins in complex assembly; NF-kappaB essential modulator coordinates some IKK complexes, whereas TANK, NF-kappaB-activating kinase-associated protein 1 (NAP1) or similar to NAP1 TBK1 adaptor (SINTBAD) assemble TBK1 and IKK-epsilon complexes. The different scaffold proteins undergo similar post-translational modifications, including phosphorylation and non-degradative polyubiquitylation. Moreover, increasing evidence indicates that distinct scaffold proteins assemble IKK, and potentially TBK1 and IKK-epsilon subcomplexes, in a stimulus-specific manner, which might be a mechanism to achieve specificity.
Chau
Tieu-Lan
TL
Interdisciplinary Cluster for Applied Genoproteomics, University of Liège, Sart-Tilman, 4000 Liège, Belgium.
Gioia
Romain
R
Gatot
Jean-Stéphane
JS
Patrascu
Félicia
F
Carpentier
Isabelle
I
Chapelle
Jean-Paul
JP
O'Neill
Luke
L
Beyaert
Rudi
R
Piette
Jacques
J
Chariot
Alain
A
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D016328:NF-kappa B; C524349:TBKBP1 protein, human; D025801:Ubiquitin; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase