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.
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Authors | Jennifer 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 |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 289
Issue 10
Pg. 6429-6437
(Mar 07 2014)
ISSN: 1083-351X [Electronic] United States |
PMID | 24407287
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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