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Articles

Clock gene affect the noncanonical NF-κB pathway via circadian variation of Otud7b

, , , , , , , , , , , , & show all
Pages 939-950 | Received 17 Apr 2017, Accepted 21 Apr 2017, Published online: 25 May 2017
 

Abstract

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-κB. Thus, understanding the mechanisms by which circadian clocks regulate NF-κB is a necessary step toward the development of improved therapies underwritten by NF-κB manipulation. Previous reports have identified OTUD7B a deubiquitinase, as a novel regulator of noncanonical NF-κB signaling, largely through the maintenance of TRAF3, a negative regulator of NF-κB. 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-κB pathway regulation.

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