TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures.

Nadine Tarantino 1 Jean-Yves Tinevez 2 Elizabeth Faris Crowell 3 Bertrand Boisson 4 Ricardo Henriques 5, 6, 7 Musa Mhlanga 6, 8 Fabrice Agou 1 Alain Israël 1 Emmanuel Laplantine 1, *
* Auteur correspondant
1 SMAC - Signalisation Moléculaire et Activation Cellulaire
2 PFID - Imagerie Dynamique (Plate-Forme)
3 Trafic membranaire et Division cellulaire
4 The Rockefeller University [New-York]
5 Imagerie et Modélisation
6 Instituto de Medicina Molecular
7 UCL - University College of London [London]
8 CSIR - Council for Scientific and Industrial Research [Pretoria]
Abstract : 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.
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Journal of Cell Biology, Rockefeller University Press, 2014, 204 (2), pp.231-45. 〈10.1083/jcb.201307172〉
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Nadine Tarantino, Jean-Yves Tinevez, Elizabeth Faris Crowell, Bertrand Boisson, Ricardo Henriques, et al.. TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures.. Journal of Cell Biology, Rockefeller University Press, 2014, 204 (2), pp.231-45. 〈10.1083/jcb.201307172〉. 〈pasteur-01539965〉

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