Signaling to survive: linear ubiquitination in health and disease

Abstract Post-translational modification with ubiquitin (Ub) controls protein stability, localization and function and occurs as single entity, or as poly-Ub chains, linked via lysine residues or the N-terminal methionine (M1 poly-Ub). Generated by the linear ubiquitin chain assembly complex (LUBAC) and counteracted by the deubiquitinating enzymes OTULIN and CYLD, M1 poly-Ub controls immune signaling, survival and cell death. Here, we discuss old and new functions of M1 poly-Ub in health and disease.