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Updated: Aug 12, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Duck MARCH8 Negatively Regulates the RLR Signaling Pathway through K29-Linked Polyubiquitination of MAVS
Zuxian Chen1,2, Yingying Wang1, Yating Song1
1College of Veterinary Medicine, Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China; and.
Abstract:
Mitochondrial antiviral signaling protein (MAVS) is a key adaptor in cellular innate immunity. Ubiquitination plays an important role in regulating MAVS-mediated innate immune responses; however, the molecular mechanisms underlying ubiquitination of MAVS have not been fully elucidated. In this study, we first identified the mitochondria-resident E3 ligase duck membrane-associated RING-CH 8 (duMARCH8) in ducks as a negative regulator of duck MAVS (duMAVS). Overexpression of duMARCH8 impaired the duMAVS-mediated signaling pathway, whereas knockdown of duMARCH8 resulted in the opposite effects. The suppression was due to duMARCH8 interacting with duMAVS and degrading it in a proteasome-dependent manner. We further found that duMARCH8 interacted with the 176-619 regions of duMAVS. Moreover, duMARCH8 catalyzed the K29-linked polyubiquitination of duMAVS at Lys 398 to inhibit the MAVS-mediated signaling pathway. Collectively, our findings reveal a new strategy involving MARCH8 that targets the retinoic acid-inducible gene-I-like receptor signaling pathway to regulate innate immune responses in ducks.
Insights
Duck MARCH8 E3 ligase targets duck MAVS for degradation, inhibiting innate immunity. This study reveals a novel mechanism regulating antiviral signaling pathways in ducks.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Mitochondrial antiviral signaling protein (MAVS) is crucial for innate immunity.
- Ubiquitination regulates MAVS-mediated immune responses, but mechanisms are unclear.
Purpose of the Study:
- Identify regulators of duck MAVS (duMAVS) ubiquitination.
- Elucidate the role of E3 ligases in duMAVS innate immune signaling.
Main Methods:
- Identified duck MARCH8 (duMARCH8) as an E3 ligase.
- Investigated duMARCH8 interaction with duMAVS using overexpression and knockdown.
- Analyzed duMAVS degradation via proteasome-dependent pathways.
- Determined ubiquitination site and linkage type.
Main Results:
- duMARCH8 negatively regulates duMAVS signaling.
- duMARCH8 interacts with and degrades duMAVS proteasome-dependently.
- duMARCH8 catalyzes K29-linked polyubiquitination of duMAVS at Lys 398.
- duMARCH8 inhibits the retinoic acid-inducible gene-I-like receptor signaling pathway.
Conclusions:
- Duck MARCH8 is a novel negative regulator of duMAVS.
- MARCH8-mediated ubiquitination of duMAVS inhibits innate immune responses.
- This pathway offers a new target for regulating antiviral immunity in ducks.
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