title: Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53.
abstract: 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 Domain1α (DD1α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α 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. DD1α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Kyoung Wan
authors.initials: KW
authors.lastname: Yoon
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Sanguine
authors.initials: S
authors.lastname: Byun
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Eunjeong
authors.initials: E
authors.lastname: Kwon
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Hwang
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Kiki
authors.initials: K
authors.lastname: Chu
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hiraki
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Jo
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weins
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Samy
authors.initials: S
authors.lastname: Hakroush
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Angelika
authors.initials: A
authors.lastname: Cebulla
authors.affiliation: Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Sykes
authors.affiliation: Department of Medicine, Glom-NExT Center for Glomerular Kidney Disease and Novel Experimental Therapeutics, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Greka
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Fisher
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Mandinova
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. swlee@mgh.harvard.edu.
authors.forename: Sam W
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D060887:B7 Antigens; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000276:immunology*; D010718:Phosphatidylserines / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D060887:B7 Antigens; D008565:Membrane Proteins; D010718:Phosphatidylserines; D016159:Tumor Suppressor Protein p53; C000588758:VSIR protein, human; C548983:Vsir protein, mouse