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

First Author  Yoon KW Year  2015
Journal  Science Volume  349
Issue  6247 Pages  1261669
PubMed ID  26228159 Mgi Jnum  J:223648
Mgi Id  MGI:5660009 Doi  10.1126/science.1261669
Citation  Yoon KW, et al. (2015) CELL DEATH. Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science 349(6247):1261669
abstractText  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 Domain1alpha (DD1alpha), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1alpha 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. DD1alpha-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1alpha thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.
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