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American Association of Immunologists, The Journal of Immunology, 6(185), p. 3127-3130, 2010

DOI: 10.4049/jimmunol.1001512

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Cutting Edge: Proteolytic Inactivation of Poly(ADP-Ribose) Polymerase 1 by the Nlrp3 and Nlrc4 Inflammasomes

Journal article published in 2010 by R. K. Subbarao Malireddi ORCID, Sirish Ippagunta, Mohamed Lamkanfi, Thirumala-Devi Kanneganti ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract 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.