STING-mediated degradation of IFI16 negatively regulates apoptosis by inhibiting p53 phosphorylation at serine 392
| Autor: | Yanghua Qin, Feng Ma, Fan Zhang, Jingfei Zhu, Lifen Xie, Sudan He, Dapei Li, Zigang Qiao, Liang Li, Fangrong Shen, Shengchuan Chen, Sanyue Mai, Haiping Yao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
p53
0301 basic medicine Lung Neoplasms Apoptosis Biochemistry NSCLC non–small cell lung cancer PYD PYRIN domain Carcinoma Non-Small-Cell Lung p53-luc a p53 luciferase reporter Drosophila Proteins HRP horse radish peroxidase Phosphorylation Ser392 serine 392 biology Chemistry CDDP cisplatin Nuclear Proteins HIN hematopoietic expression IFN-inducible and nuclear location Cell biology Stimulator of interferon genes Research Article Signal Transduction IFI16 interferon-γ–inducible factor 16 STING stimulator of interferon genes PKR protein kinase R IFN-I type I IFN 03 medical and health sciences mitochondrial membrane potential Bcl-2-associated X protein Cell Line Tumor Humans IFN interferon p53 upregulated modulator of apoptosis IFI16 Protein kinase A Molecular Biology PUMA p53 upregulated modulator of apoptosis MDM2 murine double minute 2 030102 biochemistry & molecular biology Ser15 serine 15 Membrane Proteins Cell Biology HEK293T human embryonic kidney 293T Phosphoproteins Protein kinase R Immunity Innate eye diseases BAX Bcl-2–associated X protein Sting 030104 developmental biology biology.protein Tumor Suppressor Protein p53 STING DAPI 4′ 6-diamidino-2-phenylindole |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.100930 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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