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

Diana Saleiro, Gavin T. Blyth, Ewa M. Kosciuczuk, Patrick A. Ozark, Beata Majchrzak-Kita, Ahmet D. Arslan, Mariafausta Fischietti, Neha K. Reddy, Curt M. Horvath, Roger J. Davis, Eleanor N. Fish, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Article numberaap9921
JournalScience Signaling
Volume11
Issue number557
DOIs
StatePublished - Nov 20 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Saleiro, D., Blyth, G. T., Kosciuczuk, E. M., Ozark, P. A., Majchrzak-Kita, B., Arslan, A. D., Fischietti, M., Reddy, N. K., Horvath, C. M., Davis, R. J., Fish, E. N., & Platanias, L. C. (2018). IFN--inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5. Science Signaling, 11(557), [aap9921]. https://doi.org/10.1126/scisignal.aap9921