Targeting WDR5: A WINning Anti-Cancer Strategy?
Autor: | April M. Weissmiller, William P. Tansey, Erin R. Aho, Stephen W. Fesik |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Histone H3 Lysine 4 Cancer therapy WDR5 lcsh:QH426-470 epigenetic mechanisms MYC Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Histone methylation Genetics medicine histone methylation Epigenetics Cancer Methylation medicine.disease small molecule inhibitors 3. Good health Chromatin lcsh:Genetics 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Commentary Cancer research chromatin |
Zdroj: | Epigenetics Insights, Vol 12 (2019) Epigenetics Insights |
ISSN: | 2516-8657 |
Popis: | WDR5 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. |
Databáze: | OpenAIRE |
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