Inhibition of Wnt signaling by Dishevelled PDZ peptides.

Nature chemical biology ·Vol. 5 ·No. 4 ·2009-04-00 ·Pages 217-9

Zhang Y, Appleton BA, Wiesmann C, Lau T, Costa M, Hannoush RN, Sidhu SS

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

Chemicals

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

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Zhang Yingnan

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

Appleton Brent A

Wiesmann Christian

Lau Ted

Costa Mike

Hannoush Rami N

Sidhu Sachdev S

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18 references, click to expand

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Article Info

Journal

Nature chemical biology

Abbr.

Nat Chem Biol

ISSN

1552-4469

DOI

10.1038/nchembio.152

Published

2009-04-00

Epub

2009-00-01

Pages

217-9

Language

English

Region

United States

NLM ID

101231976

Subset

Databases

PubChem-Substance

56479562

External Links

PubMed source DOI: 10.1038/nchembio.152 View journal details

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Inhibition of Wnt signaling by Dishevelled PDZ peptides.

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