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dc.contributor.authorThompson, David B.
dc.contributor.authorVillaseñor, Roberto
dc.contributor.authorDorr, B
dc.contributor.authorZerial, Marino
dc.contributor.authorLiu, David Ruchien
dc.date.accessioned2016-06-28T17:39:21Z
dc.date.issued2012
dc.identifier.citationThompson, David B., Roberto Villaseñor, Brent M. Dorr, Marino Zerial, and David R. Liu. 2012. Cellular uptake mechanisms and endosomal trafficking of supercharged proteins. Chemistry & Biology 19, no. 7: 831–843. doi:10.1016/j.chembiol.2012.06.014.en_US
dc.identifier.issn1074-5521en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27409158
dc.description.abstractSupercharged proteins can deliver functional macromolecules into the cytoplasm of mammalian cells with potencies that exceed those of cationic peptides. The structural features of supercharged proteins that determine their delivery effectiveness and the intracellular fate of supercharged proteins once they enter cells have not yet been studied. Using a large set of supercharged GFP(scGFP) variants, we found that the level of cellular uptake is sigmoidally related to net charge, and that scGFPs enter cells through multiple pathways including clathrin-dependent endocytosis and macropinocytosis. Supercharged proteins activate Rho and ERK1/2, and also alter the endocytic transport of transferrin and EGF. Finally, we discovered that the intracellular trafficking of endosomes containing scGFPs is altered in a manner that correlates with protein delivery potency. Collectively, our findings establish basic structure-activity relationships of supercharged proteins and implicate the modulation of endosomal trafficking as a determinant of cell-penetration and macromolecule-delivery efficiency.en_US
dc.description.sponsorshipChemistry and Chemical Biologyen_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.chembiol.2012.06.014en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408882/en_US
dash.licenseOAP
dc.subjectproteinsen_US
dc.subjectcellsen_US
dc.subjectepidermal growth factoren_US
dc.subjectpeptidesen_US
dc.subjectcells (biology)en_US
dc.subjectepidermal growth factorsen_US
dc.subjectbiological sciencesen_US
dc.titleCellular uptake mechanisms and endosomal trafficking of supercharged proteinsen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalChemistry & Biologyen_US
dash.depositing.authorLiu, David Ruchien
dc.date.available2016-06-28T17:39:21Z
dash.funder.nameUS National Intitute of General Medical Sciencesen_US
dash.funder.awardR01GM065400en_US
dash.funder.awardR01GM095501en_US
dc.identifier.doi10.1016/j.chembiol.2012.06.014*
dash.contributor.affiliatedDorr, B
dash.contributor.affiliatedLiu, David


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