FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2494823100> ?p ?o ?g. }

• W2494823100 abstract "Metabolic genes are increasingly recognized as targets of somatic genetic alteration in human cancer often leading to profound changes in intracellular metabolite concentrations. 5-Methylthioadenosine Phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway that metabolizes methylthioadenosine (MTA) to adenine and methionine. Its chromosomal position proximal to CDKN2A results in frequent collateral homozygous deletion in a wide range of human cancers. By interrogating data from a large scale deep-coverage pooled shRNA screen across 390 cancer cell line models we found that the viability of MTAP null cancer cells is strongly impaired upon shRNA-mediated depletion of the protein arginine methyltransferase PRMT5. In MTAP deleted cells there is marked accumulation of the substrate MTA and surprisingly, we find that MTA is a specific inhibitor of the catalytic activity of PRMT5. In keeping with these data, knockout of MTAP in an MTAP-proficient cell line led to increased MTA levels and rendered them sensitive to PRMT5 depletion. Moreover, reconstitution of MTAP in an MTAP-deficient cell line fully rescued PRMT5 dependence. Collectively, these findings indicate that the collateral loss of MTAP in CDNK2A deleted cancers leads to accumulation of MTA that thereby creates a hypomorphic PRMT5 state that is selectively sensitized towards further PRMT5 inhibition. Citation Format: Konstantinos Mavrakis, E Robert McDonald III, Michael R. Schlabach, Eric Billy, Gregory R. Hoffman, Antoine deWeck, David A. Ruddy, Kavitha Venkatesan, Greg McAllister, Rosalie deBeaumont, Samuel Ho, Yue Liu, Yan Yan-Neale, Guizhi Yang, Fallon Lin, Hong Yin, Hui Gao, David Randal Kipp, Songping Zhao, Joshua T. McNamara, Elizabeth R. Sprague, Young Shin Cho, Justin Gu, Ken Crawford, Vladimir Capka, Kristen Hurov, Jeffrey A. Porter, John Tallarico, Craig Mickanin, Emma Lees, Raymond Pagliarini, Nicholas Keen, Tobias Schmelzle, Francesco Hofmann, Frank Stegmeier, William R. Sellers. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to marked dependence on PRMT5. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-017." @default.
• W2494823100 created "2016-08-23" @default.
• W2494823100 creator A5001937247 @default.
• W2494823100 creator A5004088923 @default.
• W2494823100 creator A5005072713 @default.
• W2494823100 creator A5006137580 @default.
• W2494823100 creator A5011776488 @default.
• W2494823100 creator A5013578775 @default.
• W2494823100 creator A5017077218 @default.
• W2494823100 creator A5020337361 @default.
• W2494823100 creator A5026781698 @default.
• W2494823100 creator A5029615166 @default.
• W2494823100 creator A5031577912 @default.
• W2494823100 creator A5034658859 @default.
• W2494823100 creator A5034969903 @default.
• W2494823100 creator A5036314552 @default.
• W2494823100 creator A5036448564 @default.
• W2494823100 creator A5051454670 @default.
• W2494823100 creator A5055781521 @default.
• W2494823100 creator A5057024955 @default.
• W2494823100 creator A5057333101 @default.
• W2494823100 creator A5057346782 @default.
• W2494823100 creator A5060650383 @default.
• W2494823100 creator A5062067947 @default.
• W2494823100 creator A5066467082 @default.
• W2494823100 creator A5069634653 @default.
• W2494823100 creator A5074446717 @default.
• W2494823100 creator A5079255608 @default.
• W2494823100 creator A5079859545 @default.
• W2494823100 creator A5084455368 @default.
• W2494823100 creator A5085639687 @default.
• W2494823100 creator A5086937383 @default.
• W2494823100 creator A5087335353 @default.
• W2494823100 creator A5088024162 @default.
• W2494823100 creator A5088132041 @default.
• W2494823100 creator A5088209122 @default.
• W2494823100 creator A5089363087 @default.
• W2494823100 creator A5089863595 @default.
• W2494823100 date "2016-07-15" @default.
• W2494823100 modified "2023-09-27" @default.
• W2494823100 title "Abstract LB-017: Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to marked dependence on PRMT5" @default.
• W2494823100 doi "https://doi.org/10.1158/1538-7445.am2016-lb-017" @default.
• W2494823100 hasPublicationYear "2016" @default.
• W2494823100 type Work @default.
• W2494823100 sameAs 2494823100 @default.
• W2494823100 citedByCount "1" @default.
• W2494823100 countsByYear W24948231002021 @default.
• W2494823100 crossrefType "proceedings-article" @default.
• W2494823100 hasAuthorship W2494823100A5001937247 @default.
• W2494823100 hasAuthorship W2494823100A5004088923 @default.
• W2494823100 hasAuthorship W2494823100A5005072713 @default.
• W2494823100 hasAuthorship W2494823100A5006137580 @default.
• W2494823100 hasAuthorship W2494823100A5011776488 @default.
• W2494823100 hasAuthorship W2494823100A5013578775 @default.
• W2494823100 hasAuthorship W2494823100A5017077218 @default.
• W2494823100 hasAuthorship W2494823100A5020337361 @default.
• W2494823100 hasAuthorship W2494823100A5026781698 @default.
• W2494823100 hasAuthorship W2494823100A5029615166 @default.
• W2494823100 hasAuthorship W2494823100A5031577912 @default.
• W2494823100 hasAuthorship W2494823100A5034658859 @default.
• W2494823100 hasAuthorship W2494823100A5034969903 @default.
• W2494823100 hasAuthorship W2494823100A5036314552 @default.
• W2494823100 hasAuthorship W2494823100A5036448564 @default.
• W2494823100 hasAuthorship W2494823100A5051454670 @default.
• W2494823100 hasAuthorship W2494823100A5055781521 @default.
• W2494823100 hasAuthorship W2494823100A5057024955 @default.
• W2494823100 hasAuthorship W2494823100A5057333101 @default.
• W2494823100 hasAuthorship W2494823100A5057346782 @default.
• W2494823100 hasAuthorship W2494823100A5060650383 @default.
• W2494823100 hasAuthorship W2494823100A5062067947 @default.
• W2494823100 hasAuthorship W2494823100A5066467082 @default.
• W2494823100 hasAuthorship W2494823100A5069634653 @default.
• W2494823100 hasAuthorship W2494823100A5074446717 @default.
• W2494823100 hasAuthorship W2494823100A5079255608 @default.
• W2494823100 hasAuthorship W2494823100A5079859545 @default.
• W2494823100 hasAuthorship W2494823100A5084455368 @default.
• W2494823100 hasAuthorship W2494823100A5085639687 @default.
• W2494823100 hasAuthorship W2494823100A5086937383 @default.
• W2494823100 hasAuthorship W2494823100A5087335353 @default.
• W2494823100 hasAuthorship W2494823100A5088024162 @default.
• W2494823100 hasAuthorship W2494823100A5088132041 @default.
• W2494823100 hasAuthorship W2494823100A5088209122 @default.
• W2494823100 hasAuthorship W2494823100A5089363087 @default.
• W2494823100 hasAuthorship W2494823100A5089863595 @default.
• W2494823100 hasConcept C104317684 @default.
• W2494823100 hasConcept C111819275 @default.
• W2494823100 hasConcept C121608353 @default.
• W2494823100 hasConcept C153911025 @default.
• W2494823100 hasConcept C173396325 @default.
• W2494823100 hasConcept C185592680 @default.
• W2494823100 hasConcept C190232843 @default.
• W2494823100 hasConcept C2780265364 @default.
• W2494823100 hasConcept C2780912031 @default.
• W2494823100 hasConcept C33288867 @default.
• W2494823100 hasConcept C502942594 @default.
• W2494823100 hasConcept C515207424 @default.
• W2494823100 hasConcept C54355233 @default.
• W2494823100 hasConcept C55493867 @default.
• W2494823100 hasConcept C81885089 @default.
• W2494823100 hasConcept C86803240 @default.

• next