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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.
AuthorsJennifer K Dowling, Christine E Becker, Nollaig M Bourke, Sinead C Corr, Dympna J Connolly, Susan R Quinn, Paolo P Pandolfi, Ashley Mansell, Luke A J O'Neill
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 10 Pg. 6429-6437 (Mar 07 2014) ISSN: 1083-351X [Electronic] United States
PMID24407287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AIM2 protein, human
  • CARD Signaling Adaptor Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nuclear Proteins
  • PYCARD protein, human
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
Topics
  • CARD Signaling Adaptor Proteins
  • Carrier Proteins (metabolism)
  • Cell Line, Tumor
  • Cell Nucleus (metabolism)
  • Cytoskeletal Proteins (genetics, metabolism)
  • Cytosol (metabolism)
  • DNA-Binding Proteins
  • HEK293 Cells
  • Humans
  • Inflammasomes (metabolism)
  • Macrophages (metabolism)
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nuclear Proteins (genetics, metabolism)
  • Promyelocytic Leukemia Protein
  • Protein Multimerization
  • Transcription Factors (genetics, metabolism)
  • Tumor Suppressor Proteins (genetics, metabolism)

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