Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation

Jennifer K Dowling, Christine Becker, Nollaig Bourke, Sinead C Corr, Dympna J Connolly, Susan R Quinn, Pier Paolo Pandolfi, Ashley Scott Mansell, Luke A J O'Neill

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9 Citations (Scopus)

Abstract

The apoptosis-associated speck-like protein containing a caspase-activating recruitment domain (ASC) is an essential component of several inflammasomes, multiprotein complexes that regulate caspase-1 activation and inflammation. We report here an interaction between promyelocytic leukemia protein (PML) and ASC. We observed enhanced formation of ASC dimers in PML-deficient macrophages. These macrophages also display enhanced levels of ASC in the cytosol. Furthermore, IL-1beta production was markedly enhanced in these macrophages in response to both NLRP3 and AIM2 inflammasome activation and following bone marrow-derived macrophage infection with herpes simplex virus-1 (HSV-1) and Salmonella typhimurium. Collectively, our data indicate that PML limits ASC function, retaining ASC in the nucleus.
Original languageEnglish
Pages (from-to)6429 - 6437
Number of pages9
JournalJournal of Biological Chemistry
Volume289
Issue number10
DOIs
Publication statusPublished - 2014

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