Ubiquitous points of control over regulatory T cells.
Ubiquitous points of control over regulatory T cells.
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DOI：
10.1007/s00109-014-1156-z
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发表时间：
2014-06
影响因子：
4.7
通讯作者：
Barbi, Joseph
中科院分区：
文献类型：
--
作者：
Pan, Fan;Barbi, Joseph
泛素标记的翻译后修饰对于调节许多靶蛋白的稳定性、活性和细胞定位以及包括DNA修复、细胞周期进展、蛋白质质量控制和信号转导在内的过程至关重要。长期以来人们已经认识到，泛素介导的事件对于导致白细胞活化和刺激效应子功能的某些信号传导途径是重要的。现在很清楚，免疫调节的分子和途径的活动也通过泛素进行修饰和调节。在免疫控制的机制中，调节性T细胞（或T细胞）本身对这种调节特别敏感。E3连接酶和去泛素化酶都通过其对与这些细胞相关的信号通路的作用或通过Foxp3的直接翻译后调节来影响TclO。在这篇综述中，我们将总结和讨论几个例子，泛素介导的控制多个方面的生物学的Tendon，包括他们的产生，功能和表型保真度。充分探索和利用，这些调节Treg的潜在机会可能会导致新的免疫疗法，用于免疫抑制的积极和消极微调。
Posttranslational modification by ubiquitin tagging is crucial for regulating the stability, activity and cellular localization of many target proteins and processes including DNA repair, cell cycle progression, protein quality control and signal transduction. It has long been appreciated that ubiquitin-mediated events are important for certain signaling pathways leading to leukocyte activation and the stimulation of effector function. It is now clear that the activities of molecules and pathways central to immune regulation are also modified and regulated through ubiquitin. Among the mechanisms of immune control, regulatory T cells (or Tregs) are themselves particularly sensitive to such regulation. E3 ligases and deubiquitinases both influence Tregs through their effects on signaling pathways pertinent for these cells or through the direct, posttranslational regulation of Foxp3. In this review we will summarize and discuss several examples of ubiquitin-mediated control over multiple aspects of biology of Tregs including their generation, function and phenotypic fidelity. Fully explored and exploited, these potential opportunities for Treg modulation may lead to novel immunotherapies for both positive and negative fine-tuning of immune restraint.
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