PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4.

You F; Sun H; Zhou X; Sun W; Liang S; Zhai Z; Jiang Z

doi:10.1038/ni.1815

PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4.

You F ¹,

Sun H ,

Zhou X ,

Sun W ,

Liang S ,

Zhai Z ,

Jiang Z

Affiliations

1. The Education Ministry Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.
Authors
You F¹
(1 author)

ORCIDs linked to this article

Nature Immunology, 01 Nov 2009, 10(12):1300-1308
https://doi.org/10.1038/ni.1815 PMID: 19881509

Abstract

MAVS is critical in innate antiviral immunity as the sole adaptor for RIG-I-like helicases. MAVS regulation is essential for the prevention of excessive harmful immune responses. Here we identify PCBP2 as a negative regulator in MAVS-mediated signaling. Overexpression of PCBP2 abrogated cellular responses to viral infection, whereas knockdown of PCBP2 exerted the opposite effect. PCBP2 was induced after viral infection, and its interaction with MAVS led to proteasomal degradation of MAVS. PCBP2 recruited the HECT domain-containing E3 ligase AIP4 to polyubiquitinate and degrade MAVS. MAVS was degraded after viral infection in wild-type mouse embryonic fibroblasts but remained stable in AIP4-deficient (Itch(-/-)) mouse embryonic fibroblasts, coupled with greatly exaggerated and prolonged antiviral responses. The PCBP2-AIP4 axis defines a new signaling cascade for MAVS degradation and 'fine tuning' of antiviral innate immunity.

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References

Articles referenced by this article (39)

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Gene Ontology Annotation Project

https://www.ebi.ac.uk/QuickGO/annotations?reference=19881509

Proteins in UniProt (Showing 5 of 58)

K Homology domain-containing protein(UniProt - A0A2R8VI15)
K Homology domain-containing protein(UniProt - A0A2R8VHL8)
K Homology domain-containing protein(UniProt - A0A2R8VHN3)
K Homology domain-containing protein(UniProt - A0A2R8VHP9)
K Homology domain-containing protein(UniProt - A0A2R8VHZ0)

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GlyGen is an international glycobioinformatics knowledgebase funded by The National Institutes of Health to facilitate glycoscience research by integrating diverse kinds of information, including glycomics, genomics, proteomics (and glycoproteomics), cell biology, developmental biology and biochemistry.

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Mouse Genome Informatics (MGI)

http://www.informatics.jax.org/reference/19881509

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Search life-sciences literature (45,103,589 articles, preprints and more)

PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4.

Affiliations

Authors

ORCIDs linked to this article

Abstract

Full text links

References

ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization.

Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain.

Characterisation of the nucleic-acid-binding activity of KH domains. Different properties of different domains.

Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation.

Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.

CD14 is required for MyD88-independent LPS signaling.

An mRNA stability complex functions with poly(A)-binding protein to stabilize mRNA in vitro.

The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch.

Mechanisms underlying ubiquitination.

Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125.

Citations & impact

Impact metrics

Citations of article over time

Alternative metrics

Article citations

HNF4A-AS1 inhibits the progression of hepatocellular carcinoma by promoting the ubiquitin-modulated degradation of PCBP2 and suppressing the stability of ARG2 mRNA.

The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation.

Overexpression of long noncoding RNA DUXAP8 inhibits ER-phagy through activating AKT/mTOR signaling and contributes to preeclampsia.

MAVS Cys508 palmitoylation promotes its aggregation on the mitochondrial outer membrane and antiviral innate immunity.

The Hemagglutinin of Influenza A Virus Induces Ferroptosis to Facilitate Viral Replication.

Data

Data that cites the article

Gene Ontology Annotation Project

Proteins in UniProt (Showing 5 of 58)

Mouse Genome Informatics (MGI)

SIGNOR

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Search life-sciences literature (45,103,589 articles, preprints and more)

PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4.

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Abstract

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Gene Ontology Annotation Project

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Mouse Genome Informatics (MGI)

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