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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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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. |
format | Online Article Text |
id | pubmed-8851536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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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