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STING-mediated degradation of IFI16 negatively regulates apoptosis by inhibiting p53 phosphorylation at serine 392.
Li, Dapei; Xie, Lifen; Qiao, Zigang; Mai, Sanyue; Zhu, Jingfei; Zhang, Fan; Chen, Shengchuan; Li, Liang; Shen, Fangrong; Qin, Yanghua; Yao, Haiping; He, Sudan; Ma, Feng.
Afiliación
  • Li D; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China. Electronic address: dapei_1173@163.com.
  • Xie L; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Qiao Z; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Mai S; Department of Laboratory Medicine, 988 Central Hospital of People's Liberation Army, Zhengzhou, China.
  • Zhu J; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Zhang F; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Chen S; Suzhou Institute of Systems Medicine, Suzhou, China; Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Li L; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China; Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medica
  • Shen F; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Qin Y; Department of Laboratory Diagnosis, Changhai Hospital of the Second Military Medical University, Shanghai, China.
  • Yao H; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
  • He S; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
  • Ma F; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China; Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medica
J Biol Chem ; 297(2): 100930, 2021 08.
Article en En | MEDLINE | ID: mdl-34216619
Interferon-γ-inducible factor 16 (IFI16) triggers stimulator of interferon (IFN) genes (STING)-dependent type I IFN production during host antiviral immunity and facilitates p53-dependent apoptosis during suppressing tumorigenesis. We have previously reported that STING-mediated IFI16 degradation negatively regulates type I IFN production. However, it is unknown whether STING also suppresses IFI16/p53-dependent apoptosis via degradation of IFI16. Here, our results from flow cytometry apoptosis detection and immunoblot assays show that IFI16 and nutlin-3, a p53 pathway activator, synergistically induce apoptosis in U2OS and A549 cells. Protein kinase R-triggered phosphorylation of p53 at serine 392 is critical for the IFI16-p53-dependent apoptosis. However, overexpression of STING suppresses p53 serine 392 phosphorylation, p53 transcriptional activity, expression of p53 target genes, and p53-dependent mitochondrial depolarization and apoptosis. In summary, our current study demonstrates that STING-mediated IFI16 degradation negatively regulates IFI16-mediated p53-dependent apoptosis in osteosarcoma and non-small cell lung cancer cells, which suggests a protumorigenic role for STING in certain cancer types because of its potent ability to degrade upstream IFI16.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteínas Nucleares / Proteína p53 Supresora de Tumor / Proteínas de la Membrana Límite: Humans Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteínas Nucleares / Proteína p53 Supresora de Tumor / Proteínas de la Membrana Límite: Humans Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos