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.

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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