Molecular control of the NEMO family of ubiquitin-binding proteins

Research over the past decade has revealed how NF-kappa B essential modulator (NEMO; also known as IKK gamma) regulates the IKK alpha-IKK beta signalling axis in the innate immune system. The discovery that NEMO is a polyubiquitin-binding protein and that the IKK complex is modulated by other protein kinases that are themselves controlled by polyubiquitin chains has provided a deeper molecular understanding of the non-degradative roles of ubiquitylation. New mechanistic insights of NEMO and related polyubiquitin-binding proteins have become a paradigm for how the interplay between phosphorylation and ubiquitylation controls cell signalling networks in health and disease.