Wang Kezhou, Zhou Wei, Cai Qi, Cheng Jinke, Cai Rong, Xing Rong
a Department of Biochemistry and Molecular Cell Biology , Shanghai Jiaotong University School of Medicine , Shanghai , China.
b Department of Pathophysiology , Dalian Medical University , Dalian , China.
Cell Cycle. 2017 Feb 16;16(4):374-381. doi: 10.1080/15384101.2016.1269045. Epub 2017 Jan 6.
Macrophages, in response to different environmental cues, undergo the classical polarization (M1 macrophages) as well as the alternative polarization (M2 macrophages) that involve the functions of stimulus-specific transcription factors. Kruppel-like factor 4 (KLF4), a member of a subfamily of the zinc-finger class of DNA-binding transcription factors, plays as a critical regulator of macrophage polarization. KLF4 has been reported as a SUMOylated protein. In this study, we showed that SUMOylation of KLF4, is induced by IL-4 treatment in macrophages. IL4-induced KLF4 SUMOylation promotes RAW264.7 cells and bone marrow derived macrophages (BMDMs) to polarize into M2 subset. Thus, we identified an important post-translational modification (PTM), SUMOylation, plays a crucial role in regulating KLF4 activity during IL-4 induced macrophage M2 polarization. SUMOylation of KLF4 can be a potential therapeutic target in the resolution of inflammation.
巨噬细胞根据不同的环境线索，经历经典极化（M1巨噬细胞）以及涉及刺激特异性转录因子功能的替代性极化（M2巨噬细胞）。Kruppel样因子4（KLF4）是DNA结合转录因子锌指类亚家族的成员，作为巨噬细胞极化的关键调节因子发挥作用。KLF4已被报道为一种SUMO化蛋白。在本研究中，我们表明巨噬细胞经白细胞介素-4（IL-4）处理可诱导KLF4的SUMO化。IL-4诱导的KLF4 SUMO化促进RAW264.7细胞和骨髓来源的巨噬细胞（BMDM）极化为M2亚群。因此，我们确定了一种重要的翻译后修饰（PTM）——SUMO化，在IL-4诱导的巨噬细胞M2极化过程中调节KLF4活性方面起着关键作用。KLF4的SUMO化可能是炎症消退中的一个潜在治疗靶点。
