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

• 作者: Qi Yang Jielin Tang Chonghui Xu He Zhao Yuan Zhou Yanyi Wang Min Yang Xinwen Chen Jizheng Chen
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（12）
• 所属期刊栏目: Articles
• 页码范围: 933-945
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/jmcb/mjaa043

摘要

Protein modification by small ubiquitin-like modifier(SUMO)is an important regulatory mechanism for multiple cellular pro-cesses.Although the canonical pathway involving the ubiquitylation or phosphorylation of IκBα has been well characterized,lit-tle is known about the sumoylation of IκBα in the control of NF-κB activity.Here,we find that histone deacetylase 4(HDAC4)neg-atively 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 be-cause these two modifications occur both at the Lys21.Our findings reveal a previously undiscovered role for HDAC4 in the in-flammatory response as a SUMO E3 ligase for IκBα sumoylation.Our work provides insight into mechanisms ensuring optimal mediation of the NF-κB pathway.