| First Author | Okazaki T | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 388 | Pages | ra78 |
| PubMed ID | 26243192 | Mgi Jnum | J:258562 |
| Mgi Id | MGI:6142111 | Doi | 10.1126/scisignal.aab1883 |
| Citation | Okazaki T, et al. (2015) The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response. Sci Signal 8(388):ra78 |
| abstractText | Viral infection activates host defense mechanisms, including the production of type I interferon (IFN) and the apoptosis of infected cells. We investigated whether these two antiviral responses were differentially regulated in infected cells. We showed that the mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) apoptosis signal-regulating kinase 1 (ASK1) was activated in cells by the synthetic double-stranded RNA analog polyinosinic:polycytidylic acid [poly(I:C)] and by RNA viruses, and that ASK1 played an essential role in both the induction of the gene encoding IFN-beta (IFNB) and apoptotic cell death. In contrast, we found that the MAPKKK ASK2, a modulator of ASK1 signaling, was essential for ASK1-dependent apoptosis, but not for inducing IFNB expression. Furthermore, genetic deletion of either ASK1 or ASK2 in mice promoted the replication of influenza A virus in the lung. These results indicated that ASK1 and ASK2 are components of the antiviral defense mechanism and suggested that ASK2 acts as a key modulator that promotes apoptosis rather than the type I IFN response. Because ASK2 is selectively present in epithelium-rich tissues, such as the lung, ASK2-dependent apoptosis may contribute to an antiviral defense in tissues with a rapid repair rate in which cells could be readily replaced. |
