Inhibition of Wnt signaling by Dishevelled PDZ peptides

被引:133
作者
Zhang, Yingnan [1 ]
Appleton, Brent A. [1 ]
Wiesmann, Christian [1 ]
Lau, Ted [2 ]
Costa, Mike [2 ]
Hannoush, Rami N. [1 ]
Sidhu, Sachdev S. [1 ]
机构
[1] Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Canc Targets & Pathways, San Francisco, CA 94080 USA
关键词
BETA-CATENIN; TRANSCRIPTIONAL ACTIVITY; DOMAIN; SPECIFICITY; PATHWAY; OVEREXPRESSION; ANTAGONIST; ACTIVATION; PROTEINS; CANCER;
D O I
10.1038/nchembio.152
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:217 / 219
页数:3
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