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
• 机 构: Department of Gastroenterology,Guangzhou Women and Children’s Medical Center,Guangzhou 510623,China
• 出 处: 分子细胞生物学报（英文版）
• 发表日期: 2020年12期
• 关键词: histone deacetylase 4 sumoylation IκBα NF-κB SUMO E3 ligase

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.