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dc.contributor.authorOhba, Shigeo
dc.contributor.authorJohannessen, Tor-Christian Aase
dc.contributor.authorChatla, Kamalakar
dc.contributor.authorYang, Xiaodong
dc.contributor.authorPieper, Russell O.
dc.contributor.authorMukherjee, Joydeep
dc.date.accessioned2021-06-24T06:08:14Z
dc.date.available2021-06-24T06:08:14Z
dc.date.created2021-02-15T13:21:28Z
dc.date.issued2020
dc.identifier.issn2211-1247
dc.identifier.urihttps://hdl.handle.net/11250/2760979
dc.description.abstractThe metabolic enzyme phosphoglycerate mutase 1 (PGAM1) is overexpressed in several types of cancer, suggesting an additional function beyond its established role in the glycolytic pathway. We here report that PGAM1 is overexpressed in gliomas where it increases the efficiency of the DNA damage response (DDR) pathway by cytoplasmic binding of WIP1 phosphatase, thereby preventing WIP1 nuclear translocation and subsequent dephosphorylation of the ATM signaling pathway. Silencing of PGAM1 expression in glioma cells consequently decreases formation of γ-H2AX foci, increases apoptosis, and decreases clonogenicity following irradiation (IR) and temozolomide (TMZ) treatment. Furthermore, mice intracranially implanted with PGAM1-knockdown cells have significantly improved survival after treatment with IR and TMZ. These effects are counteracted by exogenous expression of two kinase-dead PGAM1 mutants, H186R and Y92F, indicating an important non-enzymatic function of PGAM1. Our findings identify PGAM1 as a potential therapeutic target in gliomas.en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titlePhosphoglycerate Mutase 1 Activates DNA Damage Repair via Regulation of WIP1 Activityen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 The Authorsen_US
dc.source.articlenumber107518en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.1016/j.celrep.2020.03.082
dc.identifier.cristin1889898
dc.source.journalCell Reportsen_US
dc.identifier.citationCell Reports. 2020, 31 (2), 107518.en_US
dc.source.volume31en_US
dc.source.issue2en_US


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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