STAT6
巨噬细胞极化
串扰
乙酰转移酶
乙酰化
细胞生物学
生物
极化(电化学)
免疫系统
巨噬细胞
化学
免疫学
白细胞介素4
生物化学
物理
体外
光学
基因
物理化学
作者
Tao Yu,Shucheng Gan,Qingchen Zhu,Dongfang Dai,Li Ni,Hui Wang,Xiaosong Chen,Dan Hou,Yan Wang,Qiang Pan,Jing Xu,Xingli Zhang,Junli Liu,Siyu Pei,Chao Peng,Ping Wu,Simona Romano,Chaoming Mao,Mingzhu Huang,Xiaoyan Zhu,Kunwei Shen,Jun Qin,Yichuan Xiao
标识
DOI:10.1038/s41467-019-12384-2
摘要
Abstract Stat6 is known to drive macrophage M2 polarization. However, how macrophage polarization is fine-tuned by Stat6 is poorly understood. Here, we find that Lys383 of Stat6 is acetylated by the acetyltransferase CREB-binding protein (CBP) during macrophage activation to suppress macrophage M2 polarization. Mechanistically, Trim24, a CBP-associated E3 ligase, promotes Stat6 acetylation by catalyzing CBP ubiquitination at Lys119 to facilitate the recruitment of CBP to Stat6. Loss of Trim24 inhibits Stat6 acetylation and thus promotes M2 polarization in both mouse and human macrophages, potentially compromising antitumor immune responses. By contrast, Stat6 mediates the suppression of TRIM24 expression in M2 macrophages to contribute to the induction of an immunosuppressive tumor niche. Taken together, our findings establish Stat6 acetylation as an essential negative regulatory mechanism that curtails macrophage M2 polarization.
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