Linear ubiquitination at a glance

Ubiquitination (also known as ubiquitylation) is a post-translational modification that creates versatility in cell signalling and regulates a multitude of cellular processes. Its versatility lies in the capacity to form eight different inter-ubiquitin linkages through the seven lysine residues of ubiquitin and through its N-terminal methionine (M1). The latter, referred to as linear or M1 linkage, is created by the linear ubiquitin chain assembly complex (LUBAC), the only E3 ligase known to date that is capable of forming linear ubiquitin chains de novo Linear ubiquitin chains are crucial modulators of innate and adaptive immune responses, and act by regulating inflammatory and cell death signalling. In this Cell Science at a Glance article and the accompanying poster, we review the current knowledge on the role of LUBAC and linear ubiquitination in immune signalling and human physiology. We specifically focus on the role for LUBAC in signalling that is induced by the cytokine tumour necrosis factor (TNF) and its role in inflammation, gene activation and cell death. Furthermore, we highlight the roles of deubiquitinases (DUBs) that cleave M1 linkages and add an additional layer in the control of LUBAC-mediated immune signalling.