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

Science
Authors
Keywords
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.

Year of Publication
2015
Journal
Science
Volume
349
Issue
6247
Pages
1261669
Date Published
2015 Jul 31
ISSN
1095-9203
URL
DOI
10.1126/science.1261669
PubMed ID
26228159
PubMed Central ID
PMC5215039
Links
Grant list
R01 DK057683 / DK / NIDDK NIH HHS / United States
S10 RR027673 / RR / NCRR NIH HHS / United States
S10RR027673 / RR / NCRR NIH HHS / United States
R01 DK095045 / DK / NIDDK NIH HHS / United States
R01 DK099465 / DK / NIDDK NIH HHS / United States
DK57683 / DK / NIDDK NIH HHS / United States
R01 CA142805 / CA / NCI NIH HHS / United States
DK093378 / DK / NIDDK NIH HHS / United States
DK091218 / DK / NIDDK NIH HHS / United States
R01 DK091218 / DK / NIDDK NIH HHS / United States
R01 AR043369 / AR / NIAMS NIH HHS / United States
P01 CA080058 / CA / NCI NIH HHS / United States
CA142805 / CA / NCI NIH HHS / United States
CA149477 / CA / NCI NIH HHS / United States
R01 DK062472 / DK / NIDDK NIH HHS / United States
CA80058 / CA / NCI NIH HHS / United States
DK062472 / DK / NIDDK NIH HHS / United States