title: Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation.
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.
authors.affiliation: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Dowling
authors.affiliation: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Becker
authors.affiliation: Centre for Innate Immunity and Infectious Disease, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia.
authors.forename: Nollaig M
authors.initials: NM
authors.lastname: Bourke
authors.affiliation: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
authors.forename: Sinead C
authors.initials: SC
authors.lastname: Corr
authors.affiliation: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
authors.forename: Dympna J
authors.initials: DJ
authors.lastname: Connolly
authors.affiliation: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Quinn
authors.affiliation: Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 01605.
authors.forename: Paolo P
authors.initials: PP
authors.lastname: Pandolfi
authors.affiliation: Centre for Innate Immunity and Infectious Disease, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia.
authors.forename: Ashley
authors.initials: A
authors.lastname: Mansell
authors.affiliation: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland. Electronic address: laoneill@tcd.ie.
authors.forename: Luke A J
authors.initials: LAJ
authors.lastname: O'Neill
mesh_terms: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D055503:Protein Multimerization; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C410167:AIM2 protein, human; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009687:Nuclear Proteins; C402202:PYCARD protein, human; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human
keywords: Cancer; Cytokine; Inflammasome; Inflammation; Innate Immunity; Nod-like Receptors (NLR)