TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO–IKK supramolecular structures
Paper published in Journal of Cell Biology, January 2014
Publisher: The Rockefeller University Press
The manuscript by Tarantino et al. (2014) explores the role of NEMO, a regulatory component of the IKK complex, in NF-κB activation in response to IL-1 and TNF. The study reveals that both cytokines induce the formation of small punctate structures, enriched in activated IKKs and ubiquitinated NEMO molecules, which are anchored near the cell surface and colocalize with activated TNF receptors. The authors demonstrate that K63-linked and linear ubiquitination are required for NEMO recruitment to these structures in response to IL-1 but not TNF. Another study investigates the role of NEMO and IRAK1 in IL-1-induced NF-κB activation and finds that their ubiquitination is crucial for NEMO recruitment and subsequent NF-κB activation. The manuscript also shows that NEMO specifically recognizes K63-linked polyubiquitin chains and that this recognition is essential for NF-κB activation. Overall, the studies provide new insights into the mechanisms underlying NEMO-IKK recruitment to supramolecular structures and its role in NF-κB activation.