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Cited by 35NF-κB Signaling PathwaysUbiquitin and proteasome pathwaysGenomics and Chromatin Dynamics

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

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Yang, Qi, Tang, Jielin, Xu, Chonghui, Zhao, He, Zhou, Yuan, Wang, Yanyi, Yang, Min, Chen, Xinwen +1 more·2021·Journal of Molecular Cell Biology
DOI 10.1093/jmcb/mjaa043PMC PMC7948076
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Abstract

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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  • HDAC4 belongs to the SUMO E3 ligase family and can directly SUMOylate IκBα, AR, LXRα, and MEF2.

    “Additionally, HDAC4 belongs to the SUMO E3 ligase family and can directly SUMOylate IκBα, AR, LXRα, and MEF217–20.”

    From An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer (2026) · cites this paper as [17]

    The Results section (‘HDAC4 catalyzes the sumoylation of IκBα’; page not available) reports that HDAC4 directly mediates IκBα SUMOylation as a SUMO E3 ligase. The Introduction and Results also report HDAC4-mediated SUMOylation of LXRα and MEF2, but do not establish that it is direct; no passage found supports AR SUMOylation. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Yang, Q., Tang, J., Xu, C., Zhao, H., Zhou, Y., Wang, Y., Yang, M., Chen, X., & Chen, J.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Guangzhou Women and Children Medical Center (CN)
Corresponding author
Chen, Jizheng
ORCID
Venue
Journal of Molecular Cell Biology
Publisher
Oxford University Press (OUP)
Published
2020-12-01
Volume
12
Issue
12
Pages
933-945
ISSN
  • 1674-2788 (ISSN-L)
  • 1759-4685
DOI
10.1093/jmcb/mjaa043
PMC
PMC7948076
OpenAlex
W3047935617
Cited by
35
References
4
Citations by year
2026: 7 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 2
FWCI
1.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Cell Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2018YFA0507201, 2018YFA0507202)
  • Program for Youth Innovation Promotion Association in Chinese Academy of Sciences
  • China Postdoctoral Science Foundation (2020M672580)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
HDAC4, NF-κB activation, SUMO E3 ligase, SUMO, IκBα degradation, TNF-α, lipopolysaccharide, inflammation, cytoplasmic localization
MeSH terms
RAW 264.7 Cells, NF-KappaB Inhibitor alpha, Animals, Histone Deacetylases, Humans, Lipopolysaccharides, Recombinant Proteins, Repressor Proteins, Transfection, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Mice, HEK293 Cells, Sumoylation

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