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dc.contributor.authorParzych, Ken_US
dc.contributor.authorSaavedra-García, Pen_US
dc.contributor.authorValbuena, GNen_US
dc.contributor.authorAl-Sadah, HAen_US
dc.contributor.authorRobinson, MEen_US
dc.contributor.authorPenfold, Len_US
dc.contributor.authorKuzeva, DMen_US
dc.contributor.authorRuiz-Tellez, Aen_US
dc.contributor.authorLoaiza, Sen_US
dc.contributor.authorHolzmann, Ven_US
dc.contributor.authorCaputo, Ven_US
dc.contributor.authorJohnson, DCen_US
dc.contributor.authorKaiser, MFen_US
dc.contributor.authorKaradimitris, Aen_US
dc.contributor.authorLam, EW-Fen_US
dc.contributor.authorChevet, Een_US
dc.contributor.authorFeldhahn, Nen_US
dc.contributor.authorKeun, HCen_US
dc.contributor.authorAuner, HWen_US
dc.date.accessioned2020-06-08T15:07:39Z
dc.date.issued2019-04en_US
dc.identifier.citationOncogene, 2019, 38 (17), pp. 3216 - 3231en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3707
dc.identifier.eissn1476-5594en_US
dc.identifier.doi10.1038/s41388-018-0651-zen_US
dc.description.abstractVCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis.en_US
dc.formatPrint-Electronicen_US
dc.format.extent3216 - 3231en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectCell Line, Tumoren_US
dc.subjectHumansen_US
dc.subjectMultiple Myelomaen_US
dc.subjectProtein-Serine-Threonine Kinasesen_US
dc.subjectGlucoseen_US
dc.subjectGlutamineen_US
dc.subjectNuclear Proteinsen_US
dc.subjectSignal Transductionen_US
dc.subjectMAP Kinase Signaling Systemen_US
dc.subjectGene Expressionen_US
dc.subjectAutophagyen_US
dc.subjectAdenosine Triphosphatasesen_US
dc.subjectProteolysisen_US
dc.subjectMCF-7 Cellsen_US
dc.subjectA549 Cellsen_US
dc.subjectValosin Containing Proteinen_US
dc.subjectProteostasisen_US
dc.subjectNutrientsen_US
dc.subjectPC-3 Cellsen_US
dc.titleThe coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-12-07en_US
rioxxterms.versionofrecord10.1038/s41388-018-0651-zen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfOncogeneen_US
pubs.issue17en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublisheden_US
pubs.volume38en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorKaiser, Martinen_US
dc.contributor.icrauthorJohnson, Daviden_US


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