| Cutting edge: proteolytic inactivation of poly(ADP-ribose) polymerase 1 by the Nlrp3 and Nlrc4 inflammasomes. | |
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MedLine Citation:
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PMID: 20713892 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Caspase-mediated cleavage of the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP1) is a hallmark of apoptosis. However, it remains unclear whether PARP1 is processed during pyroptosis, a specialized cell-death program that occurs upon activation of caspase-1 in inflammasome complexes. In this article, we show that activation of the Nlrp3 and Nlrc4 inflammasomes induces processing of full-length PARP1 into a fragment of 89 kDa in a stimulus-dependent manner. Macrophages deficient for caspase-1 and those lacking the inflammasome adaptors Nlrp3, Nlrc4, and ASC were highly resistant to cleavage, whereas macrophages lacking the downstream inflammasome effector caspase-7 were partially protected. A modest, but statistically significant, reduction in Nlrp3 inflammasome-induced pyroptosis was observed in PARP1 knockout macrophages. Thus, protease-mediated inactivation of PARP1 is a shared feature of apoptotic, necrotic, and pyroptotic cells. |
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Authors:
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R K Subbarao Malireddi; Sirish Ippagunta; Mohamed Lamkanfi; Thirumala-Devi Kanneganti |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-16 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-03 Completed Date: 2010-11-23 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3127-30 Citation Subset: AIM; IM |
Affiliation:
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Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Regulatory Proteins / deficiency, genetics, physiology* Calcium-Binding Proteins / deficiency, genetics, physiology* Carrier Proteins / genetics, physiology* Caspase 1 / chemistry, physiology Caspase 7 / chemistry, physiology Cell Death / genetics, immunology Cells, Cultured Inflammation / enzymology, immunology*, pathology* Inflammation Mediators / chemistry, physiology* Mice Mice, Inbred C57BL Mice, Knockout Peptide Fragments / chemistry, metabolism Poly(ADP-ribose) Polymerases / antagonists & inhibitors*, chemistry, metabolism* Protein Processing, Post-Translational / immunology Substrate Specificity / immunology |
| Grant Support | |
ID/Acronym/Agency:
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2 P30 CA 21765/CA/NCI NIH HHS; AI088177/AI/NIAID NIH HHS; AR056296/AR/NIAMS NIH HHS; R01 AR056296-01A1/AR/NIAMS NIH HHS; R01 AR056296-03/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/CIAS1 protein, mouse; 0/Calcium-Binding Proteins; 0/Carrier Proteins; 0/Inflammation Mediators; 0/Ipaf protein, mouse; 0/Peptide Fragments; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.4.2.30/poly(ADP-ribose)polymerase-1, mouse; EC 3.4.22.-/Casp7 protein, mouse; EC 3.4.22.-/Caspase 7; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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