Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53

摘要

The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1 alpha (DD1 alpha), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1 alpha appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1 alpha-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1 alpha thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.