It is well established that activation of the transcription factor signal transducer and activator of transcription 1 (STAT1) is required for the interferon- (IFN-)-mediated antiviral response. Here, we found that IFN- receptor stimulation also activated Unc-51-like kinase 1 (ULK1), an initiator of Beclin-1-mediated autophagy. Furthermore, the interaction between ULK1 and the mitogen-activated protein kinase kinase kinase MLK3 (mixed lineage kinase 3) was necessary for MLK3 phosphorylation and downstream activation of the kinase ERK5. This autophagy-independent activity of ULK1 promoted the transcription of key antiviral IFN-stimulated genes (ISGs) and was essential for IFN--dependent antiviral effects. These findings define a previously unknown IFN- pathway that appears to be a key element of the antiviral response.
|Original language||English (US)|
|State||Published - Nov 20 2018|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology