Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death

Receptor-interacting protein 1 (RIP1) contains an amino-terminal kinase domain, a carboxy-terminal death domain and an intermediate domain with a receptor-interacting protein homotypic interaction motif (RHIM).RIP1 has emerged as a key upstream regulator that controls inflammatory signalling as well as the activation of multiple cell death pathways, including apoptosis and necroptosis.The ability of RIP1 to modulate these key cellular events is tightly controlled by ubiquitylation, deubiquitylation and the interaction of RIP1 with a class of ubiquitin receptors.Ubiquitylation of RIP1 might provide a unique 'ubiquitin code' that determines whether a cell activates cell survival through the nuclear factor-κB (NF-κB)-dependent or -independent pathways or induces cell death through necroptosis or apoptosis.Targeting RIP1 kinase might provide novel therapeutics for the treatment of both acute and chronic human diseases.