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- Title
NEMO oligomerization in the dynamic assembly of the IκB kinase core complex.
- Authors
Fontan, Elisabeth; Traincard, François; Levy, Samuel G.; Yamaoka, Shoji; Véron, Michel; Agou, Fabrice
- Abstract
NF-κB essential modulator (NEMO) plays an essential role in the nuclear factor κB (NF-κB) pathway as a modulator of the two other subunits of the IκB kinase (IKK) complex, i.e. the protein kinases, IKKα and IKKβ. Previous reports all envision the IKK complex to be a static entity. Using glycerol-gradient ultracentrifugation, we observed stimulus-dependent dynamic IKK complex assembly. In wild-type fibroblasts, the kinases and a portion of cellular NEMO associate in a 350-kDa high-molecular-mass complex. In response to constitutive NF-κB stimulation by Tax, we observed NEMO recruitment and oligomerization to a shifted high-molecular-mass complex of 440 kDa which displayed increased IKK activity. This stimulus-dependent oligomerization of NEMO was also observed using fluorescence resonance energy transfer after a transient pulse with interleukin-1β. In addition, fully activated, dimeric kinases not bound to NEMO were detected in these Tax-activated fibroblasts. By glycerol gradient ultracentrifugation, we also showed that: (a) in fibroblasts deficient in IKKα and IKKβ, NEMO predominantly exists as a monomer; (b) in NEMO-deficient fibroblasts, IKKβ dimers are present that are less stable than IKKα dimers. Intriguingly, in resting Rat-1 fibroblasts, 160-kDa IKKα–NEMO and IKKβ–NEMO heterocomplexes were observed as well as a significant proportion of NEMO monomer. These results suggest that most NEMO molecules do not form a tripartite IKK complex with an IKKα–IKKβ heterodimer as previously reported in the literature but, instead, NEMO is able to form a complex with the monomeric forms of IKKα and IKKβ.
- Subjects
PROTEIN kinases; NF-kappa B; OLIGOMERS; FIBROBLASTS; ENERGY transfer; INTERLEUKINS
- Publication
FEBS Journal, 2007, Vol 274, Issue 10, p2540
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2007.05788.x