Inhibition of Wnt signaling by Dishevelled PDZ peptides.
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.
Zhang
Yingnan
Y
Department of Protein Engineering, Genentech, Inc, South San Francisco, California, USA.
Appleton
Brent A
BA
Wiesmann
Christian
C
Lau
Ted
T
Costa
Mike
M
Hannoush
Rami N
RN
Sidhu
Sachdev S
SS
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*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D019151:Peptide Library; D010750:Phosphoproteins; D051153:Wnt Proteins