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-1β 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.
Keywords:
Cancer; Cytokine; Inflammasome; Inflammation; Innate Immunity; Nod-like Receptors (NLR).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CARD Signaling Adaptor Proteins
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Carrier Proteins / metabolism
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Cell Line, Tumor
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Cell Nucleus / metabolism
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Cytosol / metabolism
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DNA-Binding Proteins
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HEK293 Cells
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Humans
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Inflammasomes / metabolism*
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Macrophages / metabolism
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Promyelocytic Leukemia Protein
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Protein Multimerization
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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AIM2 protein, human
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CARD Signaling Adaptor Proteins
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Carrier Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Inflammasomes
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Nuclear Proteins
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PYCARD protein, human
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Promyelocytic Leukemia Protein
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Transcription Factors
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Tumor Suppressor Proteins
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PML protein, human