Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis
Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis
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DOI：
10.1016/j.celrep.2016.03.016
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发表时间：
2016-04-12
期刊：
影响因子：
8.8
通讯作者：
Liu, Xiaolong
中科院分区：
文献类型：
--
作者：
Cui, Yu;Chen, Xufeng;Liu, Xiaolong
Uhrf 1（也称为Np 95）是DNA甲基化和组蛋白泛素化的调节因子，在胚胎发生和肿瘤发生中起重要作用。在这里，我们报告说，Uhrf 1是必不可少的不变的自然杀伤T（iNKT）细胞的发展。我们发现Uhrf 1在第1阶段iNKT细胞中显著上调。Uhrf 1的靶向破坏导致第1阶段特异性转换缺陷，这不仅通过增加细胞凋亡观察到，而且通过异常效应分化观察到，这最终导致Uhrf 1缺陷小鼠中iNKT细胞的产生受损。值得注意的是，Uhrf 1缺陷导致第1阶段iNKT细胞中Akt-mTOR信号转导的激活减弱，并且活性Akt的过表达挽救了iNKT细胞发育缺陷。总的来说，我们的研究结果表明，Uhrf 1调节Akt-mTOR信号通路是iNKT细胞发育所必需的。
Uhrf1 (also known as Np95) is a regulator of DNA methylation and histone ubiquitination and plays an important role in embryogenesis and tumorigenesis. Here, we report that Uhrf1 is essential for invariant natural killer T (iNKT) cell development. We found that Uhrf1 was significantly upregulated in stage 1 iNKT cells. Targeted disruption of Uhrf1 resulted in stage 1-specific transition defects as observed by not only increased apoptosis, but also aberrant effector differentiation, which eventually led to the impaired generation of iNKT cells in Uhrf1-deficient mice. Notably, Uhrf1 deficiency resulted in attenuated activation of Akt-mTOR signaling in stage 1 iNKT cells and overexpression of active Akt rescued iNKT cell developmental defects. Collectively, our results suggest that Uhrf1 regulation of the Akt-mTOR signaling pathway is required for iNKT cell development.