Dishevelled interacts with p65 and acts as a repressor of NF-κB-mediated transcription.
Dishevelled (Dvl) is a highly conserved protein family that plays an important role in mediating Wnt signaling 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-κB. 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-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, our 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.
Deng
Ning
N
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ye
Yanger
Y
Wang
Wei
W
Li
Lin
L
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D000072261:Dishevelled Proteins; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D016328:NF-kappa B; D010750:Phosphoproteins; C498143:RELA protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051996:Transcription Factor RelA; D051153:Wnt Proteins; D051176:beta Catenin