Lethal weapons: DAP-kinase, autophagy and cell death

Recently, DAP-kinase was identified as one of the essential regulators of autophagy, activated by signals such as cytokines and ER stress. DAP-kinase is a tumor suppressor that mediates several cell death pathways, such as apoptosis and programmed necrosis. Likewise, functional studies suggest that DAP-kinase may direct autophagy specifically towards autophagic cell death. Several recent studies have mapped DAP-kinase function to distinct stages in autophagy signaling. These include the Beclin-1/phosphatidylinositol 3-kinase (PI(3)K) complex, which is necessary for autophagosome formation, and an interaction with the LC3 binding protein, MAP1B, which may regulate vesicle trafficking. This review will summarize the functional and mechanistic studies that have linked DAP-kinase to the regulation of autophagy in general, and autophagic cell death, in particular.