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dc.contributor.authorVivanco, I
dc.contributor.authorChen, ZC
dc.contributor.authorTanos, B
dc.contributor.authorOldrini, B
dc.contributor.authorHsieh, W-Y
dc.contributor.authorYannuzzi, N
dc.contributor.authorCampos, C
dc.contributor.authorMellinghoff, IK
dc.date.accessioned2020-08-06T14:51:23Z
dc.date.issued2014-12-31
dc.identifier.citationeLife, 2014, 3
dc.identifier.issn2050-084X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3916
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/elife.03751
dc.description.abstractThe serine-threonine kinase AKT regulates proliferation and survival by phosphorylating a network of protein substrates. In this study, we describe a kinase-independent function of AKT. In cancer cells harboring gain-of-function alterations in MET, HER2, or Phosphatidyl-Inositol-3-Kinase (PI3K), catalytically inactive AKT (K179M) protected from drug induced cell death in a PH-domain dependent manner. An AKT kinase domain mutant found in human melanoma (G161V) lacked enzymatic activity in vitro and in AKT1/AKT2 double knockout cells, but promoted growth factor independent survival of primary human melanocytes. ATP-competitive AKT inhibitors failed to block the kinase-independent function of AKT, a liability that limits their effectiveness compared to allosteric AKT inhibitors. Our results broaden the current view of AKT function and have important implications for the development of AKT inhibitors for cancer.
dc.formatElectronic
dc.languageeng
dc.language.isoeng
dc.publisherELIFE SCIENCES PUBLICATIONS LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectMelanoma
dc.subjectCell Survival
dc.subjectProto-Oncogene Proteins c-akt
dc.titleA kinase-independent function of AKT promotes cancer cell survival.
dc.typeJournal Article
dcterms.dateAccepted2014-12-31
rioxxterms.versionofrecord10.7554/elife.03751
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2014-12-31
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfeLife
pubs.notesNot 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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Addictions
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Addictions
pubs.publication-statusPublished
pubs.volume3
pubs.embargo.termsNot known
icr.researchteamMolecular Addictions
dc.contributor.icrauthorVivanco, Igor


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0