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

J Biol Chem. 2014 Mar 7;289(10):6429-6437. doi: 10.1074/jbc.M113.539692. Epub 2014 Jan 9.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CARD Signaling Adaptor Proteins
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Cytosol / metabolism
  • DNA-Binding Proteins
  • HEK293 Cells
  • Humans
  • Inflammasomes / metabolism*
  • Macrophages / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Protein Multimerization
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • 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