Clock gene affect the noncanonical NF-κB pathway via circadian variation of Otud7b
Clock gene affect the noncanonical NF-κB pathway via circadian variation of Otud7b
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DOI：
10.1080/09291016.2017.1323422
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发表时间：
2017-01-01
影响因子：
1.1
通讯作者：
Wang, Zhengrong
中科院分区：
文献类型：
--
作者：
Hou, Wang;Jiang, Zhou;Wang, Zhengrong
昼夜节律系统调节生理的许多重要方面，包括对感染性物质的免疫反应，这是由转录因子NF-kappa B激活所介导的。因此，了解昼夜节律调节NF-kappa B的机制是开发以NF-kappa B操作为基础的改进疗法的必要步骤。以往的报道证实OTUD7B是一种脱泛素酶，是一种新的非规范的核因子-kappa B信号调节因子，主要通过维持核因子-kappa B的负调控因子TRAF3来实现。在我们实验室的研究中，当时钟基因被shRNA抑制时，芯片分析结果表明OTUD7B下调了。实时定量聚合酶链式反应和蛋白质印迹进一步研究表明，OTUD7B呈现出有节律性的mRNA表达。这些发现证实了OTUD7B是一个新的时钟调节基因。此外，OTUD7B可能是昼夜节律系统和非经典的核因子-kappaB途径调控之间的重要桥梁。
The circadian system regulates many important aspects of physiology, including the immune response to infectious agents, which is mediated by the activation of the transcription factor NF-kappa B. Thus, understanding the mechanisms by which circadian clocks regulate NF-kappa B is a necessary step toward the development of improved therapies underwritten by NF-kappa B manipulation. Previous reports have identified OTUD7B a deubiquitinase, as a novel regulator of noncanonical NF-kappa B signaling, largely through the maintenance of TRAF3, a negative regulator of NF-kappa B. In investigations in our laboratory, when the Clock gene was repressed by shRNA, the results of microarray analysis demonstrated that Otud7b was down-regulated. Further research by real-time PCR and western blot revealed that that Otud7b exhibits rhythmic mRNA expression. These findings confirm Otud7b as a novel clock-regulated gene. Additionally, Otud7b may be an important bridge between the circadian system and noncanonical NF-kappa B pathway regulation.