Programmed necrosis: backup to and competitor with apoptosis in the immune system

Programmed cell death is essential for the development and maintenance of the immune system and its responses to exogenous and endogenous stimuli. Studies have demonstrated that in addition to caspase-dependent apoptosis, necrosis dependent on the kinases RIP1 and RIP3 (also called necroptosis) is a major programmed cell-death pathway in development and immunity. These two programmed cell-death pathways may suppress each other, and necroptosis also serves as an alternative when caspase-dependent apoptosis is inhibited or absent. Here we summarize recent advancements that have identified the molecular mechanisms that underlie necroptosis and explore the mechanisms that regulate the interplay between apoptosis and necroptosis.