Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5
Top Cited Papers
- 11 March 2016
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 351 (6278), 1208-1213
- https://doi.org/10.1126/science.aad5944
Abstract
Tumors put in a vulnerable position: Cancer cells often display alterations in metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities that can be exploited therapeutically. A variety of human tumors show changes in methionine metabolism caused by loss of the gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis et al. and Kryukov et al. found that the loss of MTAP renders cancer cell lines sensitive to growth inhibition by compounds that suppress the activity of a specific arginine methyltransferase called PRMT5. Conceivably, drugs that inhibit PRMT5 activity could be developed into a tailored therapy for MTAP-deficient tumors. Science , this issue pp. 1208 and 1214Keywords
Funding Information
- Office of Science, Office of Basic Energy Sciences, U.S. Department of Energy (DE-AC02-06CH11357)
This publication has 28 references indexed in Scilit:
- ATARiS: Computational quantification of gene suppression phenotypes from multisample RNAi screensGenome Research, 2012
- Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferationProceedings of the National Academy of Sciences of the United States of America, 2012
- Crystal structure of the human PRMT5:MEP50 complexProceedings of the National Academy of Sciences of the United States of America, 2012
- The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivityNature, 2012
- Data processing and analysis with theautoPROCtoolboxActa Crystallographica Section D-Biological Crystallography, 2011
- Overview of theCCP4 suite and current developmentsActa Crystallographica Section D-Biological Crystallography, 2011
- An introduction to data reduction: space-group determination, scaling and intensity statisticsActa Crystallographica Section D-Biological Crystallography, 2011
- RioK1, a New Interactor of Protein Arginine Methyltransferase 5 (PRMT5), Competes with pICln for Binding and Modulates PRMT5 Complex Composition and Substrate SpecificityPublished by Elsevier BV ,2011
- Features and development of CootActa Crystallographica Section D-Biological Crystallography, 2010
- Tumorigenic activity and therapeutic inhibition of Rheb GTPaseGenes & Development, 2008