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dc.contributor.authorChu, Jenniferen_US
dc.contributor.authorGalicia-Vázquez, Gabrielaen_US
dc.contributor.authorCencic, Reginaen_US
dc.contributor.authorMills, John R.en_US
dc.contributor.authorKatigbak, Alexandraen_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorPelletier, Jerryen_US
dc.coverage.spatialUnited Statesen_US
dc.date2016-04-27
dc.date.accessioned2018-01-25T16:57:51Z
dc.date.available2018-01-25T16:57:51Z
dc.date.issued2016-06-14
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/27239032
dc.identifier.citationJennifer Chu, Gabriela Galicia-Vázquez, Regina Cencic, John R Mills, Alexandra Katigbak, John A Porco, Jerry Pelletier. "CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A.." Cell Rep, Volume 15, Issue 11, pp. 2340 - 2347.
dc.identifier.issn2211-1247
dc.identifier.urihttps://hdl.handle.net/2144/26412
dc.description.abstractTargeting translation initiation is an emerging anti-neoplastic strategy that capitalizes on de-regulated upstream MAPK and PI3K-mTOR signaling pathways in cancers. A key regulator of translation that controls ribosome recruitment flux is eukaryotic initiation factor (eIF) 4F, a hetero-trimeric complex composed of the cap binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Small molecule inhibitors targeting eIF4F display promising anti-neoplastic activity in preclinical settings. Among these are some rocaglate family members that are well tolerated in vivo, deplete eIF4F of its eIF4A helicase subunit, have shown activity as single agents in several xenograft models, and can reverse acquired resistance to MAPK and PI3K-mTOR targeted therapies. Herein, we highlight the power of using genetic complementation approaches and CRISPR/Cas9-mediated editing for drug-target validation ex vivo and in vivo, linking the anti-tumor properties of rocaglates to eIF4A inhibition.en_US
dc.description.sponsorshipR01 GM073855 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHS; MOP-106530 - CIHR; MOP-115126 - CIHRen_US
dc.format.extent2340 - 2347en_US
dc.languageengen_US
dc.relation.ispartofCell Repen_US
dc.rightsCopyright 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectScience & Technologyen_US
dc.subjectLife Sciences & Biomedicineen_US
dc.subjectCell Biologyen_US
dc.subjectTranslation initiationen_US
dc.subjectTherapeutic suppressionen_US
dc.subjectMammalian-cellsen_US
dc.subjectCanceren_US
dc.subjectRocaglimideen_US
dc.subjectSilvestrolen_US
dc.subjectProhibitinen_US
dc.subjectCRISPR/Cas9en_US
dc.subjectChemical biologyen_US
dc.subjecteIF4Aen_US
dc.subjectRocaglatesen_US
dc.subjectTranslational controlen_US
dc.subjectAllelesen_US
dc.subjectAnimalsen_US
dc.subjectBase sequenceen_US
dc.subjectBenzofuransen_US
dc.subjectCRISPR-Cas Systemsen_US
dc.subjectDrug delivery systemsen_US
dc.subjectDrug resistanceen_US
dc.subjectEukaryotic Initiation Factor-4Aen_US
dc.subjectFemaleen_US
dc.subjectGenetic locien_US
dc.subjectMiceen_US
dc.subjectMice, inbred BALB Cen_US
dc.subjectMice, nudeen_US
dc.subjectMutationen_US
dc.subjectNIH 3T3 cellsen_US
dc.subjectReproducibility of resultsen_US
dc.subjectTriterpenesen_US
dc.subjectNIH 3T3 Cellsen_US
dc.titleCRISPR-mediated drug-target validation reveals selective pharmacological inhibition of the RNA Helicase, eIF4Aen_US
dc.typeArticle
dc.identifier.doi10.1016/j.celrep.2016.05.005
dc.identifier.pmid27239032
dc.identifier.pmcidPMC5315212
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublisheden_US


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Copyright 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).