2024-03-28T08:44:51Z
https://repository.dl.itc.u-tokyo.ac.jp/oai
oai:repository.dl.itc.u-tokyo.ac.jp:00000700
2022-12-19T03:41:42Z
20:179:180
9:10:11
The ASK family kinases differentially mediate type I interferon induction and apoptosis during the antiviral response
Okazaki, Tomohiko
2586
Higuchi, Maiko
2587
Takeda, Kohsuke
2588
Iwatsuki-Horimoto, Kiyoko
2589
Kiso, Maki
2590
Miyagishi, Makoto
2591
Yanai, Hideyuki
2592
Kato, Atsushi
2593
Yoneyama, Mitsutoshi
2594
Fujita, Takashi
2595
Taniguchi, Tadatsugu
2596
Kawaoka, Yoshihiro
2597
Ichijo, Hidenori
2598
Gotoh, Yukiko
2599
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-β (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.
UTokyo Research掲載「生きるべきか死ぬべきか」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/to-be-or-not-to-be-that-is-the-question.html
UTokyo Research "To be, or not to be: That is the question" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/to-be-or-not-to-be-that-is-the-question.html
journal article
American Association for the Advancement of Science
2015-08-04
application/pdf
Science signaling
388
8
ra78
AA12315525
19450877
19379145
https://repository.dl.itc.u-tokyo.ac.jp/record/700/files/scisignal.aab1883.pdf
eng
info:doi/10.1126/scisignal.aab1883
http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/to-be-or-not-to-be-that-is-the-question.html
http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/to-be-or-not-to-be-that-is-the-question.html
http://stke.sciencemag.org/content/8/388/ra78.abstract
© 2015 Authors.