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dc.contributor.authorDeJesus, Rowenaen_US
dc.contributor.authorMoretti, Francescaen_US
dc.contributor.authorMcAllister, Gregoryen_US
dc.contributor.authorWang, Zuncaien_US
dc.contributor.authorBergman, Philen_US
dc.contributor.authorLiu, Shanmingen_US
dc.contributor.authorFrias, Elizabethen_US
dc.contributor.authorAlford, Johnen_US
dc.contributor.authorReece-Hoyes, John Sen_US
dc.contributor.authorLindeman, Aliciaen_US
dc.contributor.authorKelliher, Jenniferen_US
dc.contributor.authorRuss, Carstenen_US
dc.contributor.authorKnehr, Judithen_US
dc.contributor.authorCarbone, Walteren_US
dc.contributor.authorBeibel, Martinen_US
dc.contributor.authorRoma, Guglielmoen_US
dc.contributor.authorNg, Aylwinen_US
dc.contributor.authorTallarico, John Aen_US
dc.contributor.authorPorter, Jeffery Aen_US
dc.contributor.authorXavier, Ramnik Jen_US
dc.contributor.authorMickanin, Craigen_US
dc.contributor.authorMurphy, Leon Oen_US
dc.contributor.authorHoffman, Gregory Ren_US
dc.contributor.authorNyfeler, Beaten_US
dc.date.accessioned2016-08-09T14:53:09Z
dc.date.issued2016en_US
dc.identifier.citationDeJesus, R., F. Moretti, G. McAllister, Z. Wang, P. Bergman, S. Liu, E. Frias, et al. 2016. “Functional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62.” eLife 5 (1): e17290. doi:10.7554/eLife.17290. http://dx.doi.org/10.7554/eLife.17290.en
dc.identifier.issn2050-084Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27822255
dc.description.abstractSQSTM1 is an adaptor protein that integrates multiple cellular signaling pathways and whose expression is tightly regulated at the transcriptional and post-translational level. Here, we describe a forward genetic screening paradigm exploiting CRISPR-mediated genome editing coupled to a cell selection step by FACS to identify regulators of SQSTM1. Through systematic comparison of pooled libraries, we show that CRISPR is superior to RNAi in identifying known SQSTM1 modulators. A genome-wide CRISPR screen exposed MTOR signalling and the entire macroautophagy machinery as key regulators of SQSTM1 and identified several novel modulators including HNRNPM, SLC39A14, SRRD, PGK1 and the ufmylation cascade. We show that ufmylation regulates SQSTM1 by eliciting a cell type-specific ER stress response which induces SQSTM1 expression and results in its accumulation in the cytosol. This study validates pooled CRISPR screening as a powerful method to map the repertoire of cellular pathways that regulate the fate of an individual target protein. DOI: http://dx.doi.org/10.7554/eLife.17290.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.17290en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924995/pdf/en
dash.licenseLAAen_US
dc.subjectautophagyen
dc.subjectSQSTM1en
dc.subjectER stressen
dc.subjectCRISPRen
dc.subjectHumanen
dc.titleFunctional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62en
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorNg, Aylwinen_US
dc.date.available2016-08-09T14:53:09Z
dc.identifier.doi10.7554/eLife.17290*
dash.authorsorderedfalse
dash.contributor.affiliatedNg, Aylwin
dash.contributor.affiliatedXavier, Ramnik


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