Zhang Yingnan, Appleton Brent A, Wiesmann Christian, Lau Ted, Costa Mike, Hannoush Rami N, Sidhu Sachdev S
Department of Protein Engineering, Genentech, Inc, South San Francisco, California, USA.
Nat Chem Biol. 2009 Apr;5(4):217-9. doi: 10.1038/nchembio.152. Epub 2009 Mar 1.
Dishevelled proteins are key regulators of Wnt signaling pathways that have been implicated in the progression of human cancers. We found that the binding cleft of the Dishevelled PDZ domain is more flexible than those of canonical PDZ domains and enables recognition of both C-terminal and internal peptides. These peptide ligands inhibit Wnt/beta-catenin signaling in cells, showing that Dishevelled PDZ domains are potential targets for small-molecule cancer therapeutics.
无序蛋白是Wnt信号通路的关键调节因子，与人类癌症的进展有关。我们发现，无序蛋白PDZ结构域的结合裂隙比典型PDZ结构域的结合裂隙更具灵活性，能够识别C末端肽和内部肽。这些肽配体在细胞中抑制Wnt/β-连环蛋白信号传导，表明无序蛋白PDZ结构域是小分子癌症治疗的潜在靶点。
