Sci Signal

It is well established that activation of the transcription factor signal transducer and activator of transcription 1 (STAT1) is required for the interferon-\u3b3 (IFN-\u3b3)-mediated antiviral response. Here, we found that IFN-\u3b3 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-\u3b3-dependent antiviral effects. These findings define a previously unknown IFN-\u3b3 pathway that appears to be a key element of the antiviral response.R01 CA077816/NCI NIH HHS/National Cancer Institute/United StatesI01 CX000916/CSRD VA/Clinical Science Research & Development/United StatesS10 OD011996/ODCDC CDC HHS/Office of the Director/United StatesR01 CA161796/NCI NIH HHS/National Cancer Institute/United StatesP41 GM108569/NIGMS NIH HHS/National Institute of General Medical Sciences/United StatesR01 CA155566/NCI NIH HHS/National Cancer Institute/United StatesP30 CA060553/NCI NIH HHS/National Cancer Institute/United StatesT32 CA080621/NCI NIH HHS/National Cancer Institute/United StatesT32 CA070085/NCI NIH HHS/National Cancer Institute/United States2019-11-20T00:00:00Z30459284PMC6684240654