TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures.
Nuclear factor κB (NF-κB) essential modulator (NEMO), a regulatory component of the IκB kinase (IKK) complex, controls NF-κB activation through its interaction with ubiquitin chains. We show here that stimulation with interleukin-1 (IL-1) and TNF induces a rapid and transient recruitment of NEMO into punctate structures that are anchored at the cell periphery. These structures are enriched in activated IKK kinases and ubiquitinated NEMO molecules, which suggests that they serve as organizing centers for the activation of NF-κB. These NEMO-containing structures colocalize with activated TNF receptors but not with activated IL-1 receptors. We investigated the involvement of nondegradative ubiquitination in the formation of these structures, using cells deficient in K63 ubiquitin chains or linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination. Our results indicate that, unlike TNF, IL-1 requires K63-linked and linear ubiquitin chains to recruit NEMO into higher-order complexes. Thus, different mechanisms are involved in the recruitment of NEMO into supramolecular complexes, which appear to be essential for NF-κB activation.
Unité de Signalisation Moléculaire et Activation Cellulaire and 2 Laboratoire Trafic Membranaire et Division Cellulaire, Institut Pasteur, Centre National de la Recherche Scientifique URA 2582, Paris 75015, France.
Nadine
N
Tarantino
Jean-Yves
JY
Tinevez
Elizabeth Faris
EF
Crowell
Bertrand
B
Boisson
Ricardo
R
Henriques
Musa
M
Mhlanga
Fabrice
F
Agou
Alain
A
Israël
Emmanuel
E
Laplantine
D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000032:analysis / Q000378:metabolism*; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000032:analysis / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054875:Ubiquitination
C491731:IKBKG protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D051550:I-kappa B Kinase