Dishevelled interacts with p65 and acts as a repressor of NF-KB-mediated transcription  

作　　者：Ning Deng Yanger Ye Wei Wang Lin Li 

机构地区：[1]State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Cell Research》2010年第10期1117-1127,共11页细胞研究（英文版）

基　　金：This work was supported by the Ministry of Science and Technology of China （2010CB912100 and 2007CB914500）, the National Natural Science Foundation of China （30821065, 30930052 and 90813024）, and the Science and Technology Commission of Shanghai Municipality.

摘　　要：Dishevelled （Dvl） is a highly conserved protein family that plays an important role in mediating Wnt signal- ing from membrane to cytoplasm. Recently we reported that Dvl also functions in the nucleus by stabilizing the β-catenin/TCFs transcriptional complex. Here we describe that Dvl may function as a repressor of NF-kB. Our 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-KB 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-KB target genes is significantly enhanced when expression of Dvl is knocked down. Consistently, the expression level of a subset of NF-KB target genes is also increased after knock-down of Dvl. Moreover, our data suggest that Dvl may relieve the anti-apoptotic effect of NF-KB, thus play a role in promoting apoptosis. Therefore, this work demonstrates a novel function of Dvl in modulating NF-KB-regulated gene transcription.

关 键 词：Dishevelled （Dvl） NF-kB p65 transcriptional suppressor Wnt signaling 

分 类 号：Q75[生物学—分子生物学] Q785