Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming

Abstract Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such,...

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Autores principales:	Joshua D. Bernstock, Daniel Ye, Florian A. Gessler, Yang-ja Lee, Luca Peruzzotti-Jametti, Peter Baumgarten, Kory R. Johnson, Dragan Maric, Wei Yang, Donat Kögel, Stefano Pluchino, John M. Hallenbeck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da4f8bc42ef147c6a124478a1b68ce27
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spelling	oai:doaj.org-article:da4f8bc42ef147c6a124478a1b68ce272021-12-02T12:32:14ZTopotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming10.1038/s41598-017-07631-92045-2322https://doaj.org/article/da4f8bc42ef147c6a124478a1b68ce272017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07631-9https://doaj.org/toc/2045-2322Abstract Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations.Joshua D. BernstockDaniel YeFlorian A. GesslerYang-ja LeeLuca Peruzzotti-JamettiPeter BaumgartenKory R. JohnsonDragan MaricWei YangDonat KögelStefano PluchinoJohn M. HallenbeckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joshua D. Bernstock Daniel Ye Florian A. Gessler Yang-ja Lee Luca Peruzzotti-Jametti Peter Baumgarten Kory R. Johnson Dragan Maric Wei Yang Donat Kögel Stefano Pluchino John M. Hallenbeck Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
description	Abstract Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations.
format	article
author	Joshua D. Bernstock Daniel Ye Florian A. Gessler Yang-ja Lee Luca Peruzzotti-Jametti Peter Baumgarten Kory R. Johnson Dragan Maric Wei Yang Donat Kögel Stefano Pluchino John M. Hallenbeck
author_facet	Joshua D. Bernstock Daniel Ye Florian A. Gessler Yang-ja Lee Luca Peruzzotti-Jametti Peter Baumgarten Kory R. Johnson Dragan Maric Wei Yang Donat Kögel Stefano Pluchino John M. Hallenbeck
author_sort	Joshua D. Bernstock
title	Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
title_short	Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
title_full	Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
title_fullStr	Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
title_full_unstemmed	Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
title_sort	topotecan is a potent inhibitor of sumoylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/da4f8bc42ef147c6a124478a1b68ce27
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Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming

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