近日，Cell Research发表了生化与细胞所李林研究组关于Dishevelled蛋白参与NF-kB信号途径调节的最新研究成果。Dishevelled蛋白是Wnt信号通路中一个非常关键的调节蛋白，不仅在Wnt信号从细胞膜传递到胞内过程中起到承上启下的作用，而且近期被发现在细胞核内参与经典Wnt信号下游转录复合物的形成。
在这项研究中，李林研究组的邓宁和叶央尔等人发现，Dishevelled蛋白以一种不依赖Wnt信号的方式与NF-kB的核心分子p65在细胞核内发生相互作用，从而负调控p65介导的NF-kB活性。进一步的研究表明，Dishevelled通过抑制p65对某些靶基因（包括一些抗凋亡基因）启动子区的结合，从而使得NF-kB的抗凋亡作用受到抑制。这项工作揭示了Dishevelled蛋白的一种新功能及其作用机制，丰富了对相关信号转导网络的认识。
该研究得到来自科技部、国家基金委和上海市科委等项目的资助。
生物谷推荐原文出处：
Cell Research advance online publication 13 July 2010; doi: 10.1038/cr.2010.108
Dishevelled interacts with p65 and acts as a repressor of NF-κB-mediated transcription
Ning Deng*, Yanger Ye*, Wei Wang and Lin Li
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
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.
