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

TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 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.

Autor: Nadine Tarantino - Jean-Yves Tinevez - Elizabeth Faris Crowell - Bertrand Boisson - Ricardo Henriques - Musa Mhlanga - Fabrice Ag



Documentos relacionados