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TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa
The transcription factor NF-κB plays an important role in modulation of inflammatory pathways, which are associated with inflammatory diseases, neurodegeneration, apoptosis, immune responses, and cancer. Increasing evidence indicates that TRIM proteins are crucial role in the regulation of NF-κB sig...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901487/ https://www.ncbi.nlm.nih.gov/pubmed/35273593 http://dx.doi.org/10.3389/fimmu.2022.793147 |
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author | Fan, Wenchun Liu, Xueyan Zhang, Jinyan Qin, Liuxing Du, Jian Li, Xiangmin Qian, Suhong Chen, Huanchun Qian, Ping |
author_facet | Fan, Wenchun Liu, Xueyan Zhang, Jinyan Qin, Liuxing Du, Jian Li, Xiangmin Qian, Suhong Chen, Huanchun Qian, Ping |
author_sort | Fan, Wenchun |
collection | PubMed |
description | The transcription factor NF-κB plays an important role in modulation of inflammatory pathways, which are associated with inflammatory diseases, neurodegeneration, apoptosis, immune responses, and cancer. Increasing evidence indicates that TRIM proteins are crucial role in the regulation of NF-κB signaling pathways. In this study, we identified TRIM67 as a negative regulator of TNFα-triggered NF-κB activation. Ectopic expression of TRIM67 significantly represses TNFα-induced NF-κB activation and the expression of pro-inflammatory cytokines TNFα and IL-6. In contrast, Trim67 depletion promotes TNFα-induced expression of TNFα, IL-6, and Mcp-1 in primary mouse embryonic fibroblasts. Mechanistically, we found that TRIM67 competitively binding β-transducin repeat-containing protein (β-TrCP) to IκBα results inhibition of β-TrCP-mediated degradation of IκBα, which finally caused inhibition of TNFα-triggered NF-κB activation. In summary, our findings revealed that TRIM67 function as a novel negative regulator of NF-κB signaling pathway, implying TRIM67 might exert an important role in regulation of inflammation disease and pathogen infection caused inflammation. |
format | Online Article Text |
id | pubmed-8901487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89014872022-03-09 TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa Fan, Wenchun Liu, Xueyan Zhang, Jinyan Qin, Liuxing Du, Jian Li, Xiangmin Qian, Suhong Chen, Huanchun Qian, Ping Front Immunol Immunology The transcription factor NF-κB plays an important role in modulation of inflammatory pathways, which are associated with inflammatory diseases, neurodegeneration, apoptosis, immune responses, and cancer. Increasing evidence indicates that TRIM proteins are crucial role in the regulation of NF-κB signaling pathways. In this study, we identified TRIM67 as a negative regulator of TNFα-triggered NF-κB activation. Ectopic expression of TRIM67 significantly represses TNFα-induced NF-κB activation and the expression of pro-inflammatory cytokines TNFα and IL-6. In contrast, Trim67 depletion promotes TNFα-induced expression of TNFα, IL-6, and Mcp-1 in primary mouse embryonic fibroblasts. Mechanistically, we found that TRIM67 competitively binding β-transducin repeat-containing protein (β-TrCP) to IκBα results inhibition of β-TrCP-mediated degradation of IκBα, which finally caused inhibition of TNFα-triggered NF-κB activation. In summary, our findings revealed that TRIM67 function as a novel negative regulator of NF-κB signaling pathway, implying TRIM67 might exert an important role in regulation of inflammation disease and pathogen infection caused inflammation. Frontiers Media S.A. 2022-02-22 /pmc/articles/PMC8901487/ /pubmed/35273593 http://dx.doi.org/10.3389/fimmu.2022.793147 Text en Copyright © 2022 Fan, Liu, Zhang, Qin, Du, Li, Qian, Chen and Qian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Fan, Wenchun Liu, Xueyan Zhang, Jinyan Qin, Liuxing Du, Jian Li, Xiangmin Qian, Suhong Chen, Huanchun Qian, Ping TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa |
title | TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa |
title_full | TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa |
title_fullStr | TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa |
title_full_unstemmed | TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa |
title_short | TRIM67 Suppresses TNFalpha-Triggered NF-kB Activation by Competitively Binding Beta-TrCP to IkBa |
title_sort | trim67 suppresses tnfalpha-triggered nf-kb activation by competitively binding beta-trcp to ikba |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901487/ https://www.ncbi.nlm.nih.gov/pubmed/35273593 http://dx.doi.org/10.3389/fimmu.2022.793147 |
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