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Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation

Protein modification by small ubiquitin-like modifier (SUMO) is an important regulatory mechanism for multiple cellular processes. Although the canonical pathway involving the ubiquitylation or phosphorylation of IκBα has been well characterized, little is known about the sumoylation of IκBα in the...

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Autores principales: Yang, Qi, Tang, Jielin, Xu, Chonghui, Zhao, He, Zhou, Yuan, Wang, Yanyi, Yang, Min, Chen, Xinwen, Chen, Jizheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948076/
https://www.ncbi.nlm.nih.gov/pubmed/32770227
http://dx.doi.org/10.1093/jmcb/mjaa043
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author Yang, Qi
Tang, Jielin
Xu, Chonghui
Zhao, He
Zhou, Yuan
Wang, Yanyi
Yang, Min
Chen, Xinwen
Chen, Jizheng
author_facet Yang, Qi
Tang, Jielin
Xu, Chonghui
Zhao, He
Zhou, Yuan
Wang, Yanyi
Yang, Min
Chen, Xinwen
Chen, Jizheng
author_sort Yang, Qi
collection PubMed
description Protein modification by small ubiquitin-like modifier (SUMO) is an important regulatory mechanism for multiple cellular processes. Although the canonical pathway involving the ubiquitylation or phosphorylation of IκBα has been well characterized, little is known about the sumoylation of IκBα in the control of NF-κB activity. Here, we find that histone deacetylase 4 (HDAC4) negatively regulates tumor necrosis factor-alpha- or lipopolysaccharide-triggered NF-κB activation. HDAC4 belongs to the SUMO E3 ligase family and can directly sumoylate IκBα. The cytoplasm location of HDAC4 is essential for IκBα sumoylation. The Cys292 of HDAC4 is a key site for its SUMO E3 ligase activity. The sumoylation of IκBα prevents its polyubiquitination and degradation because these two modifications occur both at the Lys21. Our findings reveal a previously undiscovered role for HDAC4 in the inflammatory response as a SUMO E3 ligase for IκBα sumoylation. Our work provides insight into mechanisms ensuring optimal mediation of the NF-κB pathway.
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spelling pubmed-79480762021-03-16 Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation Yang, Qi Tang, Jielin Xu, Chonghui Zhao, He Zhou, Yuan Wang, Yanyi Yang, Min Chen, Xinwen Chen, Jizheng J Mol Cell Biol Articles Protein modification by small ubiquitin-like modifier (SUMO) is an important regulatory mechanism for multiple cellular processes. Although the canonical pathway involving the ubiquitylation or phosphorylation of IκBα has been well characterized, little is known about the sumoylation of IκBα in the control of NF-κB activity. Here, we find that histone deacetylase 4 (HDAC4) negatively regulates tumor necrosis factor-alpha- or lipopolysaccharide-triggered NF-κB activation. HDAC4 belongs to the SUMO E3 ligase family and can directly sumoylate IκBα. The cytoplasm location of HDAC4 is essential for IκBα sumoylation. The Cys292 of HDAC4 is a key site for its SUMO E3 ligase activity. The sumoylation of IκBα prevents its polyubiquitination and degradation because these two modifications occur both at the Lys21. Our findings reveal a previously undiscovered role for HDAC4 in the inflammatory response as a SUMO E3 ligase for IκBα sumoylation. Our work provides insight into mechanisms ensuring optimal mediation of the NF-κB pathway. Oxford University Press 2021-02-04 /pmc/articles/PMC7948076/ /pubmed/32770227 http://dx.doi.org/10.1093/jmcb/mjaa043 Text en © The Author(s) (2020). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Yang, Qi
Tang, Jielin
Xu, Chonghui
Zhao, He
Zhou, Yuan
Wang, Yanyi
Yang, Min
Chen, Xinwen
Chen, Jizheng
Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation
title Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation
title_full Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation
title_fullStr Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation
title_full_unstemmed Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation
title_short Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation
title_sort histone deacetylase 4 inhibits nf-κb activation by facilitating iκbα sumoylation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948076/
https://www.ncbi.nlm.nih.gov/pubmed/32770227
http://dx.doi.org/10.1093/jmcb/mjaa043
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