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Published on: January 12, 2020
Zw10 negatively regulates the MyD88-mediated NF-κB signaling through autophagy in teleost fish
Baolan Cao1, Ya Chen1, Junxia Cui1
1Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Abstract:
MyD88 is a typical street protein of the TLRs signaling pathway and is a central player in innate immune signaling, which can regulate the NF-κB signaling pathway and promote downstream inflammatory factors. However, studies on the molecular mechanisms of the MyD88-mediated NF-κB signaling pathway in teleosts have been poorly reported. In this study, we report that Zw10 targets MyD88 to inhibit NF-κB activation. Zw10 inhibits cell proliferation and MyD88-mediated innate immunity in fish. Zw10 interacts with MyD88, and its Δ2 domain is very critical for MyD88 degradation. In addition, we found that Zw10 degrade MyD88 by autophagy, thereby negatively regulating the MyD88-mediated NF-κB signaling pathway. This study not only enriches the research on the innate immunity of teleost fish, but also provides insights for the regulating mechanism for mammals.
Insights
Zw10 protein targets MyD88 to inhibit NF-κB activation and innate immunity in fish. This study reveals Zw10 degrades MyD88 via autophagy, impacting teleost immune signaling.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Myeloid differentiation primary response 88 (MyD88) is crucial for Toll-like receptor (TLR) signaling and innate immunity.
- The NF-κB pathway activation by MyD88 promotes inflammatory factors.
- Molecular mechanisms of MyD88-mediated NF-κB signaling in teleosts remain underexplored.
Purpose of the Study:
- To investigate the role of Zw10 in regulating Myeloid differentiation primary response 88 (MyD88)-mediated NF-κB signaling in teleosts.
- To elucidate the molecular mechanism by which Zw10 affects innate immunity.
Main Methods:
- Investigated the interaction between Zw10 and MyD88.
- Assessed the role of Zw10's Δ2 domain in MyD88 degradation.
- Examined the involvement of autophagy in Zw10-mediated MyD88 regulation.
Main Results:
- Zw10 targets and inhibits Myeloid differentiation primary response 88 (MyD88) activation of the NF-κB pathway.
- Zw10 negatively regulates cell proliferation and MyD88-dependent innate immunity in fish.
- Zw10 interacts with MyD88, with its Δ2 domain being critical for MyD88 degradation via autophagy.
Conclusions:
- Zw10 acts as a negative regulator of the Myeloid differentiation primary response 88 (MyD88)-mediated NF-κB signaling pathway in teleosts.
- Autophagy-dependent degradation of MyD88 by Zw10 is a key mechanism in innate immune regulation.
- Findings contribute to understanding teleost innate immunity and offer insights into mammalian immune regulation.
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