IFN-?-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5.

ABSTRACT: 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.

SUBMITTER: Saleiro D 

PROVIDER: S-EPMC6684240 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature