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Updated: Jul 28, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
PSMD13 inhibits NF-κB pathway by targeting TAK1 for K63-linked ubiquitination in miiuy croaker (Miichthys miiuy)
Qi Li1, Ya Chen1, Pengfei Wang1
1Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Abstract:
Transforming growth factor-β activated kinase 1 (TAK1) is an adaptor molecular in the TLR-mediated NF-κB pathway which has been implicated in the regulation of a wide range of physiological and pathological processes. Proteasome 26S subunit, non-ATPase (PSMD) 13 is essential for the structural maintenance and function of the 26S proteasome. However, the mechanism of PSMD13 in innate immune regulation is not clear. In this study, the expression of PSMD13 mRNA was significantly increased under Vibrio harveyi stimulation, and PSMD13 inhibited the NF-κB pathway by targeting TAK1. Mechanically, PSMD13 significantly inhibited the K63-linked ubiquitination of TAK1, thereby inhibiting the expression of TAK1. Moreover, this discovery enriches the research of the PSMD family in regulating the innate immune response and provides a new idea for the study of the mammalian innate immune regulation mechanism.
Insights
Proteasome 26S subunit, non-ATPase (PSMD) 13 regulates innate immunity by inhibiting the NF-κB pathway. PSMD13 targets transforming growth factor-β activated kinase 1 (TAK1), reducing its ubiquitination and expression.
Area of Science:
- Innate immunity
- Molecular biology
- Cellular signaling
Background:
- Transforming growth factor-β activated kinase 1 (TAK1) is crucial in Toll-like receptor (TLR)-mediated NF-κB signaling.
- The role of Proteasome 26S subunit, non-ATPase (PSMD) 13 in innate immune regulation remains largely unknown.
Purpose of the Study:
- To elucidate the mechanism by which PSMD13 regulates innate immunity.
- To investigate the interaction between PSMD13 and the NF-κB pathway.
Main Methods:
- Analyzing PSMD13 mRNA expression levels following Vibrio harveyi stimulation.
- Investigating the effect of PSMD13 on TAK1 ubiquitination and NF-κB pathway activity.
Main Results:
- PSMD13 mRNA expression significantly increased upon Vibrio harveyi challenge.
- PSMD13 was found to inhibit the NF-κB pathway by targeting TAK1.
- PSMD13 significantly reduced K63-linked ubiquitination of TAK1, thereby inhibiting its expression.
Conclusions:
- PSMD13 plays a regulatory role in innate immunity by inhibiting the TAK1-mediated NF-κB pathway.
- This study expands understanding of PSMD family functions in immune responses.
- Provides novel insights into mammalian innate immune regulation mechanisms.
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