NF-κB activation: nondegradative ubiquitination implicates NEMO

Non-degradative ubiquitination events have been recently demonstrated to have an important role in activating the IκB kinase (IKK) complex, the central component of the nuclear factor (NF)-κB signaling cascade. Two new papers demonstrate that NF-κB essential modulator (NEMO)–IKKγ, the structural and regulatory component of the IKK complex, specifically recognizes Lys63 polyubiquitin chains attached to the receptor-interacting protein (RIP)1 kinase following tumor necrosis factor treatment, and that this recognition is a requirement for IKK activation.