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

doi:10.1126/scisignal.aap9921

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 journal › Article › peer-review

20 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 language	English (US)
Article number	aap9921
Journal	Science Signaling
Volume	11
Issue number	557
DOIs	https://doi.org/10.1126/scisignal.aap9921
State	Published - Nov 20 2018

Funding

ASJC Scopus subject areas

Molecular Biology
Biochemistry
Cell Biology

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title = "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.",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2018 The Authors, some rights reserved.",

year = "2018",

month = nov,

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doi = "10.1126/scisignal.aap9921",

language = "English (US)",

volume = "11",

journal = "Science Signaling",

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AU - Saleiro, Diana

AU - Blyth, Gavin T.

AU - Kosciuczuk, Ewa M.

AU - Ozark, Patrick A.

AU - Majchrzak-Kita, Beata

AU - Arslan, Ahmet D.

AU - Fischietti, Mariafausta

AU - Reddy, Neha K.

AU - Horvath, Curt M.

AU - Davis, Roger J.

AU - Fish, Eleanor N.

AU - Platanias, Leonidas C.

PY - 2018/11/20

Y1 - 2018/11/20

N2 - 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.

AB - 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.

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

Abstract

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