2. Academic Validation
  3. Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53

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

  • Science. 2015 Jul 31;349(6247):1261669. doi: 10.1126/science.1261669.
Kyoung Wan Yoon 1,  Sanguine Byun 1,  Eunjeong Kwon 1,  So-Young Hwang 1,  Kiki Chu 1,  Masatsugu Hiraki 1,  Seung-Hee Jo 1,  Astrid Weins 2,  Samy Hakroush 3,  Angelika Cebulla 3,  David B Sykes 4,  Anna Greka 5,  Peter Mundel 3,  David E Fisher 1,  Anna Mandinova 6,  Sam W Lee 7
Affiliations

Affiliations

  • 1 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
  • 2 Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
  • 3 Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • 4 Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • 5 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.
  • 6 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.
  • 7 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.
PMID: 26228159 DOI: 10.1126/science.1261669
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.

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