dc.contributor.author | Parzych, K | |
dc.contributor.author | Saavedra-García, P | |
dc.contributor.author | Valbuena, GN | |
dc.contributor.author | Al-Sadah, HA | |
dc.contributor.author | Robinson, ME | |
dc.contributor.author | Penfold, L | |
dc.contributor.author | Kuzeva, DM | |
dc.contributor.author | Ruiz-Tellez, A | |
dc.contributor.author | Loaiza, S | |
dc.contributor.author | Holzmann, V | |
dc.contributor.author | Caputo, V | |
dc.contributor.author | Johnson, DC | |
dc.contributor.author | Kaiser, MF | |
dc.contributor.author | Karadimitris, A | |
dc.contributor.author | Lam, EW-F | |
dc.contributor.author | Chevet, E | |
dc.contributor.author | Feldhahn, N | |
dc.contributor.author | Keun, HC | |
dc.contributor.author | Auner, HW | |
dc.date.accessioned | 2020-06-08T15:07:39Z | |
dc.date.issued | 2019-04-25 | |
dc.identifier.citation | Oncogene, 2019, 38 (17), pp. 3216 - 3231 | |
dc.identifier.issn | 0950-9232 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3707 | |
dc.identifier.eissn | 1476-5594 | |
dc.identifier.doi | 10.1038/s41388-018-0651-z | |
dc.description.abstract | VCP/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. | |
dc.format | Print-Electronic | |
dc.format.extent | 3216 - 3231 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Multiple Myeloma | |
dc.subject | Protein-Serine-Threonine Kinases | |
dc.subject | Glucose | |
dc.subject | Glutamine | |
dc.subject | Nuclear Proteins | |
dc.subject | Signal Transduction | |
dc.subject | MAP Kinase Signaling System | |
dc.subject | Gene Expression | |
dc.subject | Autophagy | |
dc.subject | Adenosine Triphosphatases | |
dc.subject | Proteolysis | |
dc.subject | MCF-7 Cells | |
dc.subject | A549 Cells | |
dc.subject | Valosin Containing Protein | |
dc.subject | Proteostasis | |
dc.subject | Nutrients | |
dc.subject | PC-3 Cells | |
dc.title | The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-12-07 | |
rioxxterms.versionofrecord | 10.1038/s41388-018-0651-z | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncogene | |
pubs.issue | 17 | |
pubs.notes | Not known | |
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.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-status | Published | |
pubs.volume | 38 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Myeloma Group | |
dc.contributor.icrauthor | Johnson, David | |
dc.contributor.icrauthor | Kaiser, Martin | |