A novel function of Dvl in modulating NF-κB-regulated gene transcription

The research team led by Prof. Lin Li recently discovered a new function of Disheveled (Dvl) in NF-kB pathway. The researchers find that Dvl interacts with p65 and acts as a repressor of NF-κB-mediated transcription.

 

Dvl is a highly conserved protein family that plays an important role in mediating Wnt signaling from membrane to cytoplasm. The scientists in Prof. Li’s group reported that Dvl also functions in the nucleus by stabilizing the β-catenin/TCFs transcriptional complex. In their study, they find that Dvl may function as a repressor of NF-κB. Their data show that Dvl directly binds to p65 and their interaction occurs in the nucleus. Dvl expression inhibits p65-mediated or TNF-α-stimulated activation of the NF-κB dependent reporter. This action of Dvl, however, is not dependent on Wnt or its downstream effector β-catenin. Chromatin immunoprecipitation assay shows that recruitment of p65 to the promoters of NF-κB target genes is significantly enhanced when expression of Dvl is knocked down. Consistently, the expression level of a subset of NF-κB target genes is also increased after knock-down of Dvl. Moreover, their data suggest that Dvl may relieve the anti-apoptotic effect of NF-κB, thus play a role in promoting apoptosis. Therefore, this work demonstrates a novel function of Dvl in modulating NF-κB-regulated gene transcription.

 

This research was supported by the Ministry of Science and Technology, National Natural Science Foundation of China, Shanghai Municipal Commission for Science and Technology.