Cell Biology in Health and Disease Division, Institute of Molecular and Cell Biology, Proteos, Singapore 138673.
Structure. 2012 Jul 3;20(7):1135-40. doi: 10.1016/j.str.2012.04.004. Epub 2012 May 24.
The structure of the complex between the transcription cofactor Vgll1 and the transcription factor TEAD4, the mammalian equivalent of the Drosophila Vestigial and Scalloped, respectively, is determined in this study. Remarkably, Vgll1 interacts with TEAD in a manner similar to the transcription coactivators, as well as oncogenes YAP and TAZ, despite having a varied primary sequence. Vgll1-TEAD complex upregulates the expression of IGFBP-5, a proliferation-promoting gene, and facilitates anchorage-independent cell proliferation. The YAP/TAZ-TEAD complex also upregulates several other proliferation-promoting genes and also promotes anchorage-independent cell proliferation. Given its structural and functional similarity to YAP/TAZ, Vgll1 has the potential to promote cancer progression.
本研究确定了转录共激活因子 Vgll1 与转录因子 TEAD4(果蝇 Vestigial 和 Scalloped 的哺乳动物对应物)之间复合物的结构。值得注意的是,尽管 Vgll1 的一级序列存在差异,但它与 TEAD 的相互作用方式类似于转录共激活因子,以及癌基因 YAP 和 TAZ。Vgll1-TEAD 复合物上调增殖促进基因 IGFBP-5 的表达,并促进非锚定依赖性细胞增殖。YAP/TAZ-TEAD 复合物还上调其他几个增殖促进基因,并促进非锚定依赖性细胞增殖。鉴于其与 YAP/TAZ 的结构和功能相似,Vgll1 有可能促进癌症进展。