Poly(ADP-ribosyl)ation of FOXP3 Protein Mediated by PARP-1 Protein Regulates the Function of Regulatory T Cells
Poly(ADP-ribosyl)ation of FOXP3 Protein Mediated by PARP-1 Protein Regulates the Function of Regulatory T Cells
复制标题
PARP-1 蛋白介导的 FOXP3 蛋白聚（ADP-核糖基）化调节调节性 T 细胞的功能
DOI：
10.1074/jbc.m115.661611
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发表时间：
2015-11-27
影响因子：
4.8
通讯作者：
Li, Bin
中科院分区：
文献类型：
--
作者：
Luo, Xuerui;Nie, Jia;Li, Bin
聚腺苷二磷酸核糖聚合酶1（Poly（ADP-ribose）polymerase 1，PARP-1）是一种腺苷二磷酸核糖基化酶，参与多种细胞功能。然而，PARP-1在免疫系统中的作用尚未得到很好的理解。在这里，我们发现PARP-1与FOXP 3相互作用并诱导其聚（ADP-核糖基）化。通过使用PARP-1抑制剂，我们表明，减少FOXP 3的聚（ADP-核糖基）化不仅导致FOXP 3稳定和增加FOXP 3下游基因，而且还增强了调节性T细胞的抑制功能。我们的研究结果表明，PARP-1通过FOXP 3聚（ADP-核糖基）化在翻译后水平负调控Treg细胞的抑制功能。这一发现对开发PARP-1抑制剂作为预防和治疗自身免疫性疾病的潜在药物具有意义。
Poly(ADP-ribose) polymerase 1 (PARP-1) is an ADP-ribosylating enzyme participating in diverse cellular functions. The roles of PARP-1 in the immune system, however, have not been well understood. Here we find that PARP-1 interacts with FOXP3 and induces its poly(ADP-ribosyl)ation. By using PARP-1 inhibitors, we show that reduced poly(ADP-ribosyl)ation of FOXP3 results in not only FOXP3 stabilization and increased FOXP3 downstream genes but also enhanced suppressive function of regulatory T cells. Our results suggest that PARP-1 negatively regulates the suppressive function of Treg cells at the posttranslational level via FOXP3 poly(ADP-ribosyl)ation. This finding has implications for developing PARP-1 inhibitors as potential agents for the prevention and treatment of autoimmune diseases.