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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Randazzo, Paul A. Schultz, Peter G. Camp, Nathan D. Ginsberg, Mark H. Jian, Xiaoying Moon, Randall T. Major, Michael B. Ding, Sheng Zhang, Qisheng Peters, Eric C. Takanashi, Shinichi Nishiya, Naoyuki |
| Description | Author Affiliation: Zhang Q ( Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.); |
| Abstract | The Wnt/beta-catenin signaling pathway regulates cell fate and behavior during embryogenesis, adult tissue homeostasis, and regeneration. When inappropriately activated, the pathway has been linked to colorectal cancer and melanoma, and when attenuated it may contribute to Alzheimer's disease and osteoporosis. Small molecules that modulate Wnt signaling will likely provide new insights into the regulation of this key developmental pathway and ultimately provide pharmacological agents to control Wnt signaling in vivo. To this end, we screened a library of 100,000 small molecules for activity in a cell-based assay of Wnt/beta-catenin signaling and discovered a purine derivative, QS11, that synergizes with Wnt-3a ligand in the activation of Wnt/beta-catenin signal transduction. Through affinity chromatography and subsequent functional assays, we showed that QS11 binds and inhibits the GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1), suggesting that QS11 modulates Wnt/beta-catenin signaling through an effect on protein trafficking. Consistent with its function as an ARFGAP inhibitor, QS11 inhibits migration of ARFGAP overexpressing breast cancer cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 18 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Purines Pharmacology Signal Transduction Drug Effects Wnt Proteins Metabolism Beta Catenin Animals Cell Line Cell Movement Drug Evaluation, Preclinical Molecular Structure Chemistry Xenopus Laevis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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