Phosphorylation Of RIP1 Regulates Necroptosis

Necroptosis is precisely regulated.Previous studies found BHA and Amytal could block necroptosis,which led to a model that ROS is the executor of necroptosis.Recent studies demonstrate necroptosis is dependent on RIP1-RIP3-MLKL signaling cascade and MLKL translocation to cell membrane is the final step of necroptosis.By setting up necrosis ligand-free assay,we find BHA and Amytal block necroptosis by inhibiting RIPl kinase activity.RIPl kinase activity is required for necroptosis,but the underlying mechanism remains elusive.By screening for functional phosphorylation site(s)of RIPl,we identify and demonstrate that RIP1 auto-phosphorylation on Ser161 induces necroptosis.We further evaluate other functional phosphorylation sites on RIP1.