title: Inhibition of Wnt signaling by Dishevelled PDZ peptides.
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.
authors.affiliation: Department of Protein Engineering, Genentech, Inc, South San Francisco, California, USA.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Brent A
authors.initials: BA
authors.lastname: Appleton
authors.forename: Christian
authors.initials: C
authors.lastname: Wiesmann
authors.forename: Ted
authors.initials: T
authors.lastname: Lau
authors.forename: Mike
authors.initials: M
authors.lastname: Costa
authors.forename: Rami N
authors.initials: RN
authors.lastname: Hannoush
authors.forename: Sachdev S
authors.initials: SS
authors.lastname: Sidhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000072261:Dishevelled Proteins; D008958:Models, Molecular; D019151:Peptide Library; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D019151:Peptide Library; D010750:Phosphoproteins; D051153:Wnt Proteins