The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
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去泛素酶USP44通过阻止FOXP3降解来促进炎症期间Treg的功能。
DOI：
10.15252/embr.202050308
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发表时间：
2020-09-03
期刊：
影响因子：
7.7
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Yang J;Wei P;Barbi J;Huang Q;Yang E;Bai Y;Nie J;Gao Y;Tao J;Lu Y;Xie C;Hou X;Ren J;Wu X;Meng J;Zhang Y;Fu J;Kou W;Gao Y;Chen Z;Liang R;Tsun A;Li D;Guo W;Zhang S;Zheng SG;Niu J;Galardy P;Tong X;Shi G;Li H;Pan F;Li B
转录因子Forkhead box P3(FOXP3)对于调节性T细胞(Treg)的发育及其在免疫稳态中的作用是必不可少的。以往的研究表明，在天然Tregs(NTregs)中，FOXP3可以受到多泛素化和去泛素化的调节。然而，活跃在这一途径中的分子成员，特别是那些在不同的诱导Treg(ITreg)谱系中通过去泛素化来调节FOXP3的分子，仍然不清楚。在这里，我们确定泛素特异肽酶44(USP44)是一种新的FOXP3去泛素酶。USP44通过去除K48连接的泛素修饰与FOXP3相互作用并稳定FOXP3。值得注意的是，转化生长因子-β在iTreg分化过程中诱导了USP44的表达。USP44与USP7合作稳定和消除FOXP3。在炎症性疾病和癌症的多种体内模型中，缺乏USP44的Treg基因在体外和体内的多种模型中都不如野生型Tregs有效。这些发现表明，USP44在Treg功能的翻译后调节中发挥重要作用，因此是打破耐受的抗癌免疫治疗的潜在治疗靶点。泛素特异肽酶44(USP44)与FOXP3相互作用，通过去除K48连接的泛素修饰来稳定转录因子。USP44对于建立功能齐全的调节性T细胞是必不可少的。
The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin‐specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48‐linked ubiquitin modifications. Notably, TGF‐β induces USP44 expression during iTreg differentiation. USP44 co‐operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild‐type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post‐translational regulation of Treg function and is thus a potential therapeutic target for tolerance‐breaking anti‐cancer immunotherapy. The ubiquitin‐specific peptidase 44 (USP44) interacts with FOXP3 and stabilizes the transcription factor by removing K48‐linked ubiquitin modifications. USP44 is essential for the establishment of fully functional regulatory T cells.
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DOI：
10.1073/pnas.0700298104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Li, Bin;Samanta, Arabinda;Greene, Mark I.
通讯作者：
Greene, Mark I.
影响因子：
3.2
作者：
Bennett, CL;Brunkow, ME;Chance, PF
通讯作者：
Chance, PF
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
影响因子：
4.8
作者：
Luo, Xuerui;Nie, Jia;Li, Bin
通讯作者：
Li, Bin
USP21 阻止 T-helper-1 样 Treg 细胞的产生
影响因子：
16.6
作者：
Li, Yangyang;Lu, Yue;Wang, Shuaiwei;Han, Zhijun;Zhu, Fuxiang;Ni, Yingmeng;Liang, Rui;Zhang, Yan;Leng, Qibin;Wei, Gang;Shi, Guochao;Zhu, Ruihong;Li, Dan;Wang, Haikun;Zheng, Song Guo;Xu, Hongxi;Tsun, Andy;Li, Bin
通讯作者：
Li, Bin
影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY