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Activation of the cGAS-STING-IRF3 Axis by Type I and II Interferons Contributes to Host Defense.
Tong, Zhen; Zou, Jia-Peng; Wang, Su-Yun; Luo, Wei-Wei; Wang, Yan-Yi.
Afiliação
  • Tong Z; Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Zou JP; University of Chinese Academy of Sciences, Bejing, 100049, China.
  • Wang SY; Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
  • Luo WW; University of Chinese Academy of Sciences, Bejing, 100049, China.
  • Wang YY; Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Adv Sci (Weinh) ; 11(35): e2308890, 2024 Sep.
Article em En | MEDLINE | ID: mdl-39004913
ABSTRACT
Interferons (IFNs) activate JAK-STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (ß) and II (γ) IFNs are shown that can activate the transcription factor IRF3 in parallel with STAT1. IRF3-deficiency impairs transcription of a subset of downstream effector genes induced by IFN-ß and IFN-γ. Mechanistically, IFN-induced activation of IRF3 is dependent on the cGAS-STING-TBK1 axis. Both IFN-ß and IFN-γ cause mitochondrial DNA release into the cytosol. In addition, IFNs induce JAK1-mediated tyrosine phosphorylation of cGAS at Y214/Y215, which is essential for its DNA binding activity and signaling. Furthermore, deficiency of cGAS, STING, or IRF3 impairs IFN-ß- or IFN-γ-mediated antiviral and antitumor activities. The findings reveal a novel IRF3 activation pathway parallel with the canonical STAT1/2 activation pathways triggered by IFNs and provide an explanation for the pleiotropic roles of the cGAS-STING-IRF3 axis in host defense.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Fator Regulador 3 de Interferon / Proteínas de Membrana / Nucleotidiltransferases Limite: Animals / Humans Idioma: En Revista: Adv Sci (Weinh) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Fator Regulador 3 de Interferon / Proteínas de Membrana / Nucleotidiltransferases Limite: Animals / Humans Idioma: En Revista: Adv Sci (Weinh) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Alemanha