Willert K, Logan C Y, Arora A, Fish M, Nusse R
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Development. 1999 Sep;126(18):4165-73. doi: 10.1242/dev.126.18.4165.
The vertebrate Axin protein, the product of the mouse fused gene, binds to beta-catenin to inhibit Wnt signaling. We have identified a homolog of Axin in Drosophila, Daxin. Using double-stranded RNA interference, we generated loss-of-function phenotypes that are similar to overexpression of the Drosophila Wnt gene wingless (wg). Overexpression of Daxin produces phenotypes similar to loss of wg. In addition, we show that Daxin overexpression can modify phenotypes elicited by wg and another Drosophila Wnt gene, DWnt-2. Using immunoprecipitation of endogenous Daxin protein from embryos we show that Daxin interacts with Armadillo and Zeste-white 3. The loss-of-function and overexpression phenotypes show that Daxin, like its mammalian counterpart, acts as a negative regulator of wg/Wnt signaling.
脊椎动物的Axin蛋白是小鼠融合基因的产物,它与β-连环蛋白结合以抑制Wnt信号传导。我们在果蝇中鉴定出了Axin的一个同源物,即Daxin。利用双链RNA干扰技术,我们产生了与果蝇Wnt基因无翅(wg)过表达相似的功能缺失表型。Daxin的过表达产生的表型与wg缺失相似。此外,我们还表明,Daxin的过表达可以改变由wg和另一个果蝇Wnt基因DWnt-2引发的表型。通过对胚胎内源性Daxin蛋白进行免疫沉淀,我们发现Daxin与犰狳蛋白和小体白色3相互作用。功能缺失和过表达表型表明,Daxin与其哺乳动物对应物一样,作为wg/Wnt信号的负调节因子发挥作用。