Regulation of RIPK1

RIPK1 is a kinase acting downstream of death receptors and Toll like receptors to regulate cell death and inflammation. RIPK1 exhibits kinase activity dependent functions that are critical for the induction of apoptosis and necroptosis. In addition, RIPK1 exhibits kinase activity-independent scaffolding functions that are critical for preventing cell death and maintaining tissue homeostasis. Our research highlighted the important but complex role of RIPK1 in the regulation of cell death and inflammation. On the one hand, our experiments revealed that RIPK1 kinase activity-dependent apoptosis and necroptosis is a potent trigger of inflammation in vivo (Polykratis et al, JI 2014; Kondylis et al, Cancer Cell 2015, Vlantis et al, Immunity 2016). On the other hand, we found that RIPK1 acts as a scaffold to preserve tissue homeostasis by preventing apoptosis and necroptosis (Dannappel et al, Nature 2014). Our ongoing studies focus on dissecting the mechanisms regulate the kinase-dependent and -independent functions of RIPK1 and how these differentially affect tissue homeostasis in health and disease.