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

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.

Keywords:

• Circadian system
• Clock
• Otud7b
• TRAF3
• noncanonical NF-κB pathway