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TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation

Autophagy is a fundamental cellular process of protein degradation and recycling that regulates immune signaling pathways via multiple mechanisms. However, it remains unclear how autophagy epigenetically regulates the immune response. Here, we identified TRIM14 as an epigenetic regulator that reduce...

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Autores principales: Liu, Di, Zhao, Zhiyao, She, Yuanchu, Zhang, Lei, Chen, Xiangtian, Ma, Ling, Cui, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851536/
https://www.ncbi.nlm.nih.gov/pubmed/35145029
http://dx.doi.org/10.1073/pnas.2113454119
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author Liu, Di
Zhao, Zhiyao
She, Yuanchu
Zhang, Lei
Chen, Xiangtian
Ma, Ling
Cui, Jun
author_facet Liu, Di
Zhao, Zhiyao
She, Yuanchu
Zhang, Lei
Chen, Xiangtian
Ma, Ling
Cui, Jun
author_sort Liu, Di
collection PubMed
description Autophagy is a fundamental cellular process of protein degradation and recycling that regulates immune signaling pathways via multiple mechanisms. However, it remains unclear how autophagy epigenetically regulates the immune response. Here, we identified TRIM14 as an epigenetic regulator that reduces histone H3K9 trimethylation by inhibiting the autophagic degradation of the histone demethylase KDM4D. TRIM14 recruited the deubiquitinases USP14 and BRCC3 to cleave the K63-linked ubiquitin chains of KDM4D, which prevented KDM4D from undergoing optineurin (OPTN)-mediated selective autophagy. Tripartite motif-containing 14 (TRIM14) deficiency in dendritic cells significantly impaired the expression of the KDM4D-directed proinflammatory cytokines interleukin 12 (Il12) and Il23 and protected mice from autoimmune inflammation. Taken together, these findings highlight the cross-talk between epigenetic regulation and autophagy and suggest TRIM14 is a potential target of therapeutic intervention for inflammation-related diseases.
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spelling pubmed-88515362022-08-10 TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation Liu, Di Zhao, Zhiyao She, Yuanchu Zhang, Lei Chen, Xiangtian Ma, Ling Cui, Jun Proc Natl Acad Sci U S A Biological Sciences Autophagy is a fundamental cellular process of protein degradation and recycling that regulates immune signaling pathways via multiple mechanisms. However, it remains unclear how autophagy epigenetically regulates the immune response. Here, we identified TRIM14 as an epigenetic regulator that reduces histone H3K9 trimethylation by inhibiting the autophagic degradation of the histone demethylase KDM4D. TRIM14 recruited the deubiquitinases USP14 and BRCC3 to cleave the K63-linked ubiquitin chains of KDM4D, which prevented KDM4D from undergoing optineurin (OPTN)-mediated selective autophagy. Tripartite motif-containing 14 (TRIM14) deficiency in dendritic cells significantly impaired the expression of the KDM4D-directed proinflammatory cytokines interleukin 12 (Il12) and Il23 and protected mice from autoimmune inflammation. Taken together, these findings highlight the cross-talk between epigenetic regulation and autophagy and suggest TRIM14 is a potential target of therapeutic intervention for inflammation-related diseases. National Academy of Sciences 2022-02-10 2022-02-15 /pmc/articles/PMC8851536/ /pubmed/35145029 http://dx.doi.org/10.1073/pnas.2113454119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Liu, Di
Zhao, Zhiyao
She, Yuanchu
Zhang, Lei
Chen, Xiangtian
Ma, Ling
Cui, Jun
TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation
title TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation
title_full TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation
title_fullStr TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation
title_full_unstemmed TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation
title_short TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation
title_sort trim14 inhibits optn-mediated autophagic degradation of kdm4d to epigenetically regulate inflammation
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851536/
https://www.ncbi.nlm.nih.gov/pubmed/35145029
http://dx.doi.org/10.1073/pnas.2113454119
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