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Targeting WDR5: A WINning Anti-Cancer Strategy?

dc.contributor.authorAho, Erin R.
dc.contributor.authorWeissmiller, April M.
dc.contributor.authorFesik, Stephen W.
dc.contributor.authorTansey, William P.
dc.identifier.citationAho E.R., Weissmiller A.M., Fesik S.W., Tansey W.P.. Targeting WDR5: A WINning Anti-Cancer strategy. Epigenet Insights. 2019; 12:2516865719865282en_US
dc.description.abstractWDR5 is a component of multiple epigenetic regulatory complexes, including the mixed lineage leukemia (MLL)/SET complexes that deposit histone H3 lysine 4 methylation. Inhibitors of an arginine-binding cavity in WDR5, known as the WDR5-interaction (WIN) site, have been proposed to selectively kill MLL-rearranged malignancies via an epigenetic mechanism. We discovered potent WIN site inhibitors and found that they kill MLL cancer cells not through changes in histone methylation. but by displacing WDR5 from chromatin at protein synthesis genes, choking the translational capacity of these cells, and inducing death via a nucleolar stress response. The mechanism of action of WIN site inhibitors reveals new aspects of WDR5 function and forecasts broad therapeutic utility as anti-cancer agents.en_US
dc.description.sponsorshipThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: National Cancer Institute, National Institutes of Health (HHSN261200800001E to SFW; CA200709 to WPT; CA119925 to ERA and AMW); Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation (to SWF and WPT), Alex's Lemonade Stand Foundation (WPT), Edward P. Evans Foundation (WPT); Rally Foundation for Childhood Cancer Research Fellowship (AMW), Open Hands Overflowing Hearts co-funded research fellowship (AMW), the American Association for Cancer Research Basic Cancer Research Fellowship (AMW).en_US
dc.rightsCreative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (
dc.subjectCancer therapyen_US
dc.subjectepigenetic mechanismsen_US
dc.subjecthistone methylationen_US
dc.subjectsmall molecule inhibitorsen_US
dc.titleTargeting WDR5: A WINning Anti-Cancer Strategy?en_US

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