2. Academic Validation
  3. Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation

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.
Jennifer K Dowling 1,  Christine E Becker 1,  Nollaig M Bourke 2,  Sinead C Corr 1,  Dympna J Connolly 1,  Susan R Quinn 1,  Paolo P Pandolfi 3,  Ashley Mansell 2,  Luke A J O'Neill 4
Affiliations

Affiliations

  • 1 Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland.
  • 2 Centre for Innate Immunity and Infectious Disease, MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia.
  • 3 Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 01605.
  • 4 Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Pearse Street, Dublin 2, Ireland. Electronic address: laoneill@tcd.ie.
PMID: 24407287 DOI: 10.1074/jbc.M113.539692
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).

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