WIN for blocking cancer growthJan. 21, 2021, 10:00 AM
by Sarah E. Glass
WDR5 is a protein that is overexpressed in a variety of cancers. Inhibiting WDR5 by targeting the WDR5-interaction (WIN) site can inhibit the growth of cancer cells in vitro, but this mechanism of action has not been fully elucidated.
Publishing in Cell Reports, William Tansey, PhD, Alissa Guarnaccia and colleagues used quantitative proteomics to identify a collection of WIN site-sensitive WDR5 binders, bringing them one step closer to understanding WDR5’s impact on cancer.
By using an inhibitor that binds to the protein-protein interaction site on WDR5, they discovered 25 proteins that were altered in their association with WDR5, many of which have not been previously studied.
One protein, the kinase PDPK1, was found to impact expression of genes important for cell division when interacting with WDR5. These findings provide evidence for how WDR5 interactions might promote uncontrolled cell growth and how WDR5 inhibition might reverse these effects.
The research was supported by National Institutes of Health grants CA009582, CA225065, CA200709 and CA119925, as well as grants from the Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation and Edward P. Evans Foundation.