2021 Volume 97 Issue 3 Pages 120-133
Ubiquitination is a reversible post-translational modification in which ubiquitin chains are conjugated to target proteins to modulate protein function. The type of ubiquitin chain determines the mode of protein regulation. It has been shown that ubiquitin chains are formed via one of seven Lys residues in ubiquitin, and several types of ubiquitin chains are found in cells. We identified a new type of linear ubiquitin chain linked through the N-terminal Met of ubiquitin and assembled by the linear ubiquitin chain assembly complex (LUBAC), which is specific for linear chains. The discovery of linear ubiquitin chains and LUBAC is considered as a paradigm shift in ubiquitin research because linear ubiquitination is exclusive to animals, despite the existence of ubiquitination throughout eukaryotic kingdoms. Linear ubiquitination plays a critical role in immune signaling and cell death regulation. Dysregulation of LUBAC-mediated linear ubiquitination underlies various human diseases, including autoinflammation, autoimmunity, infection, and malignant tumors. This review summarizes the current status of linear ubiquitination research.