Inhibition of Wnt signaling by Dishevelled PDZ peptides

Yingnan Zhang; Brent A Appleton; Christian Wiesmann; Ted Lau; Mike Costa; Rami N Hannoush; Sachdev S Sidhu

doi:10.1038/nchembio.152

Inhibition of Wnt signaling by Dishevelled PDZ peptides

Nat Chem Biol. 2009 Apr;5(4):217-9. doi: 10.1038/nchembio.152. Epub 2009 Mar 1.

Authors

Yingnan Zhang¹, Brent A Appleton, Christian Wiesmann, Ted Lau, Mike Costa, Rami N Hannoush, Sachdev S Sidhu

Affiliation

¹ Department of Protein Engineering, Genentech, Inc, South San Francisco, California, USA.

PMID: 19252499
DOI: 10.1038/nchembio.152

Abstract

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.

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry
Adaptor Proteins, Signal Transducing / metabolism*
Dishevelled Proteins
Models, Molecular
Peptide Library
Phosphoproteins / chemistry
Phosphoproteins / metabolism*
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Signal Transduction / physiology*
Wnt Proteins / antagonists & inhibitors*

Substances

Adaptor Proteins, Signal Transducing
Dishevelled Proteins
Peptide Library
Phosphoproteins
Wnt Proteins

Associated data

PubChem-Substance/56479562