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Article: Inhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16

TitleInhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16
Authors
Issue Date2018
PublisherWiley-Blackwell Publishing Ltd. The Journal's web site is located at http://www.emboreports.org
Citation
EMBO Reports, 2018, v. 19 n. 10, article no. e45737 How to Cite?
AbstractMouse 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‐β, which has a domain architecture similar to that of mouse p202. Like p202, IFI16‐β contains two HIN domains, but lacks the pyrin domain. IFI16‐β 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‐β or phorbol ester. IFI16‐β co‐localizes with AIM2 in the cytoplasm, whereas IFI16‐α is predominantly found in the nucleus. IFI16‐β interacts with AIM2 to impede the formation of a functional AIM2‐ASC complex. In addition, IFI16‐β sequesters cytoplasmic dsDNA and renders it unavailable for AIM2 sensing. Enforced expression of IFI16‐β inhibits the activation of AIM2 inflammasome, whereas knockdown of IFI16‐β augments interleukin‐1β secretion triggered by dsDNA but not dsRNA. Thus, cytoplasm‐localized IFI16‐β is functionally equivalent to mouse p202 that exerts an inhibitory effect on AIM2 inflammasome.
Persistent Identifierhttp://hdl.handle.net/10722/259067
ISSN
2017 Impact Factor: 8.749
2015 SCImago Journal Rankings: 4.291
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, F-
dc.contributor.authorYe, Z-
dc.contributor.authorDeng, J-
dc.contributor.authorSiu, KL-
dc.contributor.authorGao, W-
dc.contributor.authorChaudhary, V-
dc.contributor.authorCheng, Y-
dc.contributor.authorFung, SY-
dc.contributor.authorYuen, KS-
dc.contributor.authorHo, TH-
dc.contributor.authorChan, CP-
dc.contributor.authorZhang, Y-
dc.contributor.authorKok, KH-
dc.contributor.authorYang, W-
dc.contributor.authorChan, CP-
dc.contributor.authorJin, D-
dc.date.accessioned2018-09-03T04:01:00Z-
dc.date.available2018-09-03T04:01:00Z-
dc.date.issued2018-
dc.identifier.citationEMBO Reports, 2018, v. 19 n. 10, article no. e45737-
dc.identifier.issn1469-221X-
dc.identifier.urihttp://hdl.handle.net/10722/259067-
dc.description.abstractMouse 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‐β, which has a domain architecture similar to that of mouse p202. Like p202, IFI16‐β contains two HIN domains, but lacks the pyrin domain. IFI16‐β 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‐β or phorbol ester. IFI16‐β co‐localizes with AIM2 in the cytoplasm, whereas IFI16‐α is predominantly found in the nucleus. IFI16‐β interacts with AIM2 to impede the formation of a functional AIM2‐ASC complex. In addition, IFI16‐β sequesters cytoplasmic dsDNA and renders it unavailable for AIM2 sensing. Enforced expression of IFI16‐β inhibits the activation of AIM2 inflammasome, whereas knockdown of IFI16‐β augments interleukin‐1β secretion triggered by dsDNA but not dsRNA. Thus, cytoplasm‐localized IFI16‐β is functionally equivalent to mouse p202 that exerts an inhibitory effect on AIM2 inflammasome.-
dc.languageeng-
dc.publisherWiley-Blackwell Publishing Ltd. The Journal's web site is located at http://www.emboreports.org-
dc.relation.ispartofEMBO Reports-
dc.titleInhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16-
dc.typeArticle-
dc.identifier.emailWang, F: wangph@hku.hk-
dc.identifier.emailYe, Z: zwye@hku.hk-
dc.identifier.emailSiu, KL: sklsfx@hkucc.hku.hk-
dc.identifier.emailCheng, Y: yuncheng@hku.hk-
dc.identifier.emailFung, SY: kittyfsy@connect.hku.hk-
dc.identifier.emailYuen, KS: samyuen@hku.hk-
dc.identifier.emailChan, CP: cpchan@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.emailChan, CP: chancp10@hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authorityChan, CP=rp02031-
dc.identifier.authorityJin, D=rp00452-
dc.description.naturepostprint-
dc.identifier.doi10.15252/embr.201845737-
dc.identifier.hkuros288520-
dc.identifier.volume19-
dc.identifier.issue10-
dc.identifier.spagee45737-
dc.identifier.epagee45737-
dc.identifier.isiWOS:000446430400009-
dc.publisher.placeUnited Kingdom-

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