Slfn2 regulates type I interferon responses by modulating the NF-κB pathway

Mariafausta Fischietti; Ahmet D. Arslan; Antonella Sassano; Diana Saleiro; Beata Majchrzak-Kita; Kazumi Ebine; Hidayatullah G. Munshi; Eleanor N. Fish; Leonidas C. Platanias

doi:10.1128/MCB.00053-18

Slfn2 regulates type I interferon responses by modulating the NF-κB pathway

Mariafausta Fischietti, Ahmet D. Arslan, Antonella Sassano, Diana Saleiro, Beata Majchrzak-Kita, Kazumi Ebine, Hidayatullah G. Munshi, Eleanor N. Fish, Leonidas C. Platanias^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Although members of the Slfn family have been implicated in the regulation of type I interferon (IFN) responses, the mechanisms by which they mediate their effects remain unknown. In the present study, we provide evidence that targeted disruption of the Slfn2 gene leads to increased transcription of IFN-stimulated genes (ISGs) and enhanced type I IFN-mediated antiviral responses. We demonstrate that Slfn2 interacts with protein phosphatase 6 regulatory subunit 1 (PPP6R1), leading to reduced type I IFN-induced activation of nuclear factor kappa B (NF-κB) signaling, resulting in reduced expression of ISGs. Altogether, these data suggest a novel mechanism by which Slfn2 controls ISG expression and provide evidence for a critical role for Slfn2 in the regulation of IFN-mediated biological responses.

Original language	English (US)
Article number	e00053-18
Journal	Molecular and cellular biology
Volume	38
Issue number	16
DOIs	https://doi.org/10.1128/MCB.00053-18
State	Published - Aug 1 2018

Funding

This work was supported in part by NIH grants CA161196, CA77816, and CA155566 and by grant I01CX000916 from the Department of Veterans Affairs. A.D.A. was supported in part by NIH/NCI grant T32 CA070085, and D.S. was supported in part by NIH/NCI grant T32 CA080621. E.N.F. is a Tier 1 Canada Research Chair in Women’s Health and Immunology. Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, and the National Resource for Translational and Developmental Proteomics, supported by P41 GM108569. Flow cytometry cell sorting was performed on a BD FACS Aria SORP system, purchased through the support of NIH 1S10OD011996-01, and this work was supported by the Northwestern University Flow Cytometry Core Facility, supported by a Cancer Center Support Grant (NCI CA060553). We declare that we have no competing financial interests.

Keywords

Antiviral responses
Interferon
NF-κB
Signal transduction
Slfn2

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/MCB.00053-18

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title = "Slfn2 regulates type I interferon responses by modulating the NF-κB pathway",

abstract = "Although members of the Slfn family have been implicated in the regulation of type I interferon (IFN) responses, the mechanisms by which they mediate their effects remain unknown. In the present study, we provide evidence that targeted disruption of the Slfn2 gene leads to increased transcription of IFN-stimulated genes (ISGs) and enhanced type I IFN-mediated antiviral responses. We demonstrate that Slfn2 interacts with protein phosphatase 6 regulatory subunit 1 (PPP6R1), leading to reduced type I IFN-induced activation of nuclear factor kappa B (NF-κB) signaling, resulting in reduced expression of ISGs. Altogether, these data suggest a novel mechanism by which Slfn2 controls ISG expression and provide evidence for a critical role for Slfn2 in the regulation of IFN-mediated biological responses.",

keywords = "Antiviral responses, Interferon, NF-κB, Signal transduction, Slfn2",

author = "Mariafausta Fischietti and Arslan, {Ahmet D.} and Antonella Sassano and Diana Saleiro and Beata Majchrzak-Kita and Kazumi Ebine and Munshi, {Hidayatullah G.} and Fish, {Eleanor N.} and Platanias, {Leonidas C.}",

note = "Funding Information: This work was supported in part by NIH grants CA161196, CA77816, and CA155566 and by grant I01CX000916 from the Department of Veterans Affairs. A.D.A. was supported in part by NIH/NCI grant T32 CA070085, and D.S. was supported in part by NIH/NCI grant T32 CA080621. E.N.F. is a Tier 1 Canada Research Chair in Women{\textquoteright}s Health and Immunology. Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, and the National Resource for Translational and Developmental Proteomics, supported by P41 GM108569. Flow cytometry cell sorting was performed on a BD FACS Aria SORP system, purchased through the support of NIH 1S10OD011996-01, and this work was supported by the Northwestern University Flow Cytometry Core Facility, supported by a Cancer Center Support Grant (NCI CA060553). We declare that we have no competing financial interests. Publisher Copyright: {\textcopyright} 2018 American Society for Microbiology.",

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doi = "10.1128/MCB.00053-18",

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AU - Fischietti, Mariafausta

AU - Arslan, Ahmet D.

AU - Sassano, Antonella

AU - Saleiro, Diana

AU - Majchrzak-Kita, Beata

AU - Ebine, Kazumi

AU - Munshi, Hidayatullah G.

AU - Fish, Eleanor N.

AU - Platanias, Leonidas C.

N1 - Funding Information: This work was supported in part by NIH grants CA161196, CA77816, and CA155566 and by grant I01CX000916 from the Department of Veterans Affairs. A.D.A. was supported in part by NIH/NCI grant T32 CA070085, and D.S. was supported in part by NIH/NCI grant T32 CA080621. E.N.F. is a Tier 1 Canada Research Chair in Women’s Health and Immunology. Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, and the National Resource for Translational and Developmental Proteomics, supported by P41 GM108569. Flow cytometry cell sorting was performed on a BD FACS Aria SORP system, purchased through the support of NIH 1S10OD011996-01, and this work was supported by the Northwestern University Flow Cytometry Core Facility, supported by a Cancer Center Support Grant (NCI CA060553). We declare that we have no competing financial interests. Publisher Copyright: © 2018 American Society for Microbiology.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Although members of the Slfn family have been implicated in the regulation of type I interferon (IFN) responses, the mechanisms by which they mediate their effects remain unknown. In the present study, we provide evidence that targeted disruption of the Slfn2 gene leads to increased transcription of IFN-stimulated genes (ISGs) and enhanced type I IFN-mediated antiviral responses. We demonstrate that Slfn2 interacts with protein phosphatase 6 regulatory subunit 1 (PPP6R1), leading to reduced type I IFN-induced activation of nuclear factor kappa B (NF-κB) signaling, resulting in reduced expression of ISGs. Altogether, these data suggest a novel mechanism by which Slfn2 controls ISG expression and provide evidence for a critical role for Slfn2 in the regulation of IFN-mediated biological responses.

AB - Although members of the Slfn family have been implicated in the regulation of type I interferon (IFN) responses, the mechanisms by which they mediate their effects remain unknown. In the present study, we provide evidence that targeted disruption of the Slfn2 gene leads to increased transcription of IFN-stimulated genes (ISGs) and enhanced type I IFN-mediated antiviral responses. We demonstrate that Slfn2 interacts with protein phosphatase 6 regulatory subunit 1 (PPP6R1), leading to reduced type I IFN-induced activation of nuclear factor kappa B (NF-κB) signaling, resulting in reduced expression of ISGs. Altogether, these data suggest a novel mechanism by which Slfn2 controls ISG expression and provide evidence for a critical role for Slfn2 in the regulation of IFN-mediated biological responses.

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KW - NF-κB

KW - Signal transduction

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ER -

Slfn2 regulates type I interferon responses by modulating the NF-κB pathway

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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