Inhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16.
EMBO Rep
; 19(10)2018 10.
Article
em En
| MEDLINE
| ID: mdl-30104205
ABSTRACT
Mouse p202 is a disease locus for lupus and a dominant-negative inhibitor of AIM2 inflammasome activation. A human homolog of p202 has not been identified so far. Here, we report a novel transcript isoform of human IFI16-designated IFI16-ß, which has a domain architecture similar to that of mouse p202. Like p202, IFI16-ß contains two HIN domains, but lacks the pyrin domain. IFI16-ß is ubiquitously expressed in various human tissues and cells. Its mRNA levels are also elevated in leukocytes of patients with lupus, virus-infected cells, and cells treated with interferon-ß or phorbol ester. IFI16-ß co-localizes with AIM2 in the cytoplasm, whereas IFI16-α is predominantly found in the nucleus. IFI16-ß interacts with AIM2 to impede the formation of a functional AIM2-ASC complex. In addition, IFI16-ß sequesters cytoplasmic dsDNA and renders it unavailable for AIM2 sensing. Enforced expression of IFI16-ß inhibits the activation of AIM2 inflammasome, whereas knockdown of IFI16-ß augments interleukin-1ß secretion triggered by dsDNA but not dsRNA Thus, cytoplasm-localized IFI16-ß is functionally equivalent to mouse p202 that exerts an inhibitory effect on AIM2 inflammasome.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Proteínas Nucleares
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas de Ligação a DNA
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Inflamassomos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article