Proteomics

Dataset Information

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AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation


ABSTRACT: Axis inhibition protein 1 (AXIN), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify AXIN acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN maintains the stability of IRF3 by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN undergoes a phase separation triggered by phosphorylated TBK1. This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN RGS domain, enhances the AXIN-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN agonist KYA1797K as an effective antiviral agent.

INSTRUMENT(S): LTQ

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver, Epithelial Cell

DISEASE(S): Liver Carcinoma

SUBMITTER: lele zhang  

LAB HEAD: Zeng Mu Sheng

PROVIDER: PXD055972 | Pride | 2024-10-31

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Hepa1-6_sgAXIN1_1_R1.raw Raw
Hepa1-6_sgAXIN1_1_R1.xlsx Xlsx
Hepa1-6_sgAXIN1_2_R1.raw Raw
Hepa1-6_sgAXIN1_2_R1.xlsx Xlsx
Hepa1-6_sgAXIN1_3_R1.raw Raw
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Publications


Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-med  ...[more]

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