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Publication

FAF1 Regulates Antiviral Immunity by Inhibiting MAVS but Is Antagonized by Phosphorylation upon Viral Infection.

Cell host & microbe | 2018

Mitochondrial antiviral signaling protein (MAVS) is an adaptor of the innate immune receptor retinoic acid-inducible gene 1 (RIG-I) that links recognition of viral RNA to antiviral signaling. Upon interacting with RIG-I, MAVS undergoes lysine 63-linked poly-ubiquitination by the E3 ligase TRIM31 and subsequently aggregates to activate downstream signaling effectors. We find that the scaffold protein FAF1 forms aggregates that negatively regulate MAVS. FAF1 antagonizes the poly-ubiquitination and aggregation of MAVS by competing with TRIM31 for MAVS association. FAF1 knockout mice are more resistant to RNA virus infection, and FAF1 deficiency in myeloid cells results in enhanced innate signaling and reduced viral load and morbidity in vivo. Upon virus infection, the kinase IKKɛ directly phosphorylates FAF1 at Ser556 and triggers FAF1 de-aggregation. Moreover, Ser556 phosphorylation promotes FAF1 lysosomal degradation, consequently relieving FAF1-dependent suppression of MAVS. These findings establish FAF1 as a modulator of MAVS and uncover mechanisms that regulate FAF1 to insure timely activation of antiviral defense.

Pubmed ID: 30472208 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.

Rabbit Anti-Human TRIM31 Antibody, Unconjugated (antibody)

RRID:AB_1858281

This unknown targets Human TRIM31

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TRAF2 (H-249) (antibody)

RRID:AB_793340

This polyclonal targets TRAF2

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VSV-g Tag Antibody (antibody)

RRID:AB_637557

This monoclonal targets VSV-g Tag

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IRF-3 (D6I4C) XP® (antibody)

RRID:AB_2722521

This monoclonal targets IRF3

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Monoclonal ANTI-FLAG® M2 antibody (antibody)

RRID:AB_259529

This monoclonal targets FLAG

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HA-probe Antibody (Y-11) (antibody)

RRID:AB_631618

This polyclonal targets HA-probe

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Mouse Anti-beta Actin - Xenopus, Drosophila and Yeast Loading Control Monoclonal Antibody, Unconjugated, Clone mAbcam 8224 (antibody)

RRID:AB_449644

This monoclonal targets beta Actin

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Mouse Anti-6X His tag Monoclonal Antibody, Unconjugated, Clone HIS.H8 (antibody)

RRID:AB_444306

This monoclonal targets 6X His tag??

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MAVS Antibody (Rodent Specific) (antibody)

RRID:AB_823566

This polyclonal targets MAVS (Rodent Specific)

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Rhodamine (TRITC)-AffiniPure Goat Anti-Mouse IgG (H+L) (min X Hu,Bov,Hrs,Rb,Sw Sr Prot) (antibody)

RRID:AB_2338488

This unknown targets Mouse IgG (H+L)

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Rabbit Anti-Human IKK-epsilon Monoclonal Antibody, Unconjugated, Clone D20G4 (antibody)

RRID:AB_1147662

This monoclonal targets Human IKK-epsilon

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Rabbit Anti-Lysine, acetyl Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_1640674

This polyclonal targets Lysine, acetyl

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Anti-Human MAVS Antibody, Unconjugated (antibody)

RRID:AB_823565

This unknown targets Human MAVS

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Phospho-IRF-3 (Ser396) (4D4G) Rabbit mAb (antibody)

RRID:AB_823547

This monoclonal targets Phospho-IRF-3 (Ser396)

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Fluorescein (FITC)-AffiniPure Goat Anti-Rabbit IgG (H+L) (antibody)

RRID:AB_2337972

This unknown targets Rabbit IgG (H+L)

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GCN5 (A-11) (antibody)

RRID:AB_10846182

This monoclonal targets GCN5 (A-11)

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Anti-mouse IgG, HRP-linked Antibody (antibody)

RRID:AB_330924

This polyclonal targets IgG

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c-Myc Antibody (9E10) (antibody)

RRID:AB_627268

This monoclonal targets c-Myc

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Rabbit Anti-Stat1, phospho (Tyr701) Monoclonal Antibody, Unconjugated, Clone 58D6 (antibody)

RRID:AB_561284

This monoclonal targets Stat1, phospho (Tyr701)

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Fluorescein (FITC)-AffiniPure Goat Anti-Mouse IgG (H+L) (min X Hu,Bov,Hrs,Rb,Sw Sr Prot) (antibody)

RRID:AB_2338599

This unknown targets Mouse IgG (H+L)

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TRAF6 (H-274) (antibody)

RRID:AB_793346

This polyclonal targets TRAF6

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Rhodamine (TRITC)-AffiniPure Goat Anti-Rabbit IgG (H+L) (antibody)

RRID:AB_2337926

This unknown targets Rabbit IgG (H+L)

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TBK1/NAK (D1B4) XP(tm) Rabbit mAb (antibody)

RRID:AB_2255663

This monoclonal targets Tbk1

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Phospho-TBK1/NAK (Ser172) (D52C2) XP Rabbit monoclonal Antibody (antibody)

RRID:AB_10693472

This monoclonal targets Phospho-TBK1/NAK (Ser172)

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Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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