近日，Cell Research發(fā)表了生化與細(xì)胞所李林研究組關(guān)于Dishevelled蛋白參與NF-kB信號途徑調(diào)節(jié)的最新研究成果,。Dishevelled蛋白是Wnt信號通路中一個非常關(guān)鍵的調(diào)節(jié)蛋白,，不僅在Wnt信號從細(xì)胞膜傳遞到胞內(nèi)過程中起到承上啟下的作用，而且近期被發(fā)現(xiàn)在細(xì)胞核內(nèi)參與經(jīng)典Wnt信號下游轉(zhuǎn)錄復(fù)合物的形成,。
在這項研究中,，李林研究組的鄧寧和葉央爾等人發(fā)現(xiàn)，Dishevelled蛋白以一種不依賴Wnt信號的方式與NF-kB的核心分子p65在細(xì)胞核內(nèi)發(fā)生相互作用,，從而負(fù)調(diào)控p65介導(dǎo)的NF-kB活性,。進(jìn)一步的研究表明，Dishevelled通過抑制p65對某些靶基因（包括一些抗凋亡基因）啟動子區(qū)的結(jié)合，從而使得NF-kB的抗凋亡作用受到抑制,。這項工作揭示了Dishevelled蛋白的一種新功能及其作用機(jī)制,，豐富了對相關(guān)信號轉(zhuǎn)導(dǎo)網(wǎng)絡(luò)的認(rèn)識。
該研究得到來自科技部,、國家基金委和上海市科委等項目的資助,。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
