| Autor: |
Oh, Sunwoo, Bournique, Elodie, Bowen, Danae, Jalili, Pégah, Sanchez, Ambrocio, Ward, Ian, Dananberg, Alexandra, Manjunath, Lavanya, Tran, Genevieve P., Semler, Bert L., Maciejowski, John, Seldin, Marcus, Buisson, Rémi |
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| Zdroj: |
Nature Communications; 8/13/2021, Vol. 12 Issue 1, p1-17, 17p |
| Abstrakt: |
APOBEC3A is a cytidine deaminase driving mutagenesis in tumors. While APOBEC3A-induced mutations are common, APOBEC3A expression is rarely detected in cancer cells. This discrepancy suggests a tightly controlled process to regulate episodic APOBEC3A expression in tumors. In this study, we find that both viral infection and genotoxic stress transiently up-regulate APOBEC3A and pro-inflammatory genes using two distinct mechanisms. First, we demonstrate that STAT2 promotes APOBEC3A expression in response to foreign nucleic acid via a RIG-I, MAVS, IRF3, and IFN-mediated signaling pathway. Second, we show that DNA damage and DNA replication stress trigger a NF-κB (p65/IkBα)-dependent response to induce expression of APOBEC3A and other innate immune genes, independently of DNA or RNA sensing pattern recognition receptors and the IFN-signaling response. These results not only reveal the mechanisms by which tumors could episodically up-regulate APOBEC3A but also highlight an alternative route to stimulate the immune response after DNA damage independently of cGAS/STING or RIG-I/MAVS. The cytidine deaminase APOBEC3A is a main source of mutagenesis in many types of cancer. Here the authors reveal that transient up-regulation of APOBEC3A and other pro-inflammatory genes can occur due to viral infection and genotoxic stress via multiple pathways. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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