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  • STING-mediated degradation of IFI16 negatively regulates apoptosis by inhibiting p53 phosphorylation at serine 392.

STING-mediated degradation of IFI16 negatively regulates apoptosis by inhibiting p53 phosphorylation at serine 392.

The Journal of biological chemistry (2021-07-04)
Dapei Li, Lifen Xie, Zigang Qiao, Sanyue Mai, Jingfei Zhu, Fan Zhang, Shengchuan Chen, Liang Li, Fangrong Shen, Yanghua Qin, Haiping Yao, Sudan He, Feng Ma
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-STING Antibody, clone S17G2C4B7, clone S17G2C4B7, from mouse
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2-Peroxidase (HRP) antibody produced in mouse, clone M2, purified immunoglobulin, buffered aqueous glycerol solution