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dc.contributor.authorHackel, Benjamin J.
dc.contributor.authorNeil, Jason Robert
dc.contributor.authorWhite, Forest M.
dc.contributor.authorWittrup, Karl Dane
dc.date.accessioned2013-07-10T13:50:45Z
dc.date.available2013-07-10T13:50:45Z
dc.date.issued2011-12
dc.date.submitted2011-09
dc.identifier.issn1741-0126
dc.identifier.issn1741-0134
dc.identifier.urihttp://hdl.handle.net/1721.1/79433
dc.description.abstractNo single engineered protein has been shown previously to robustly downregulate epidermal growth factor receptor (EGFR), a validated cancer target. A panel of fibronectin-based domains was engineered to bind with picomolar to nanomolar affinity to multiple epitopes of EGFR. Monovalent and homo- and hetero-bivalent dimers of these domains were tested for EGFR downregulation. Selected orientations of non-competitive heterodimers decrease EGFR levels by up to 80% in multiple cell types, without activating receptor signaling. These heterodimers inhibit autophosphorylation, proliferation and migration, and are synergistic with the monoclonal antibody cetuximab in these activities. These small (25 kDa) heterodimers represent a novel modality for modulating surface receptor levels.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant CA96504)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant CA118705)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Graduate Research Fellowship Program)en_US
dc.language.isoen_US
dc.publisherOxford University Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1093/protein/gzr056en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourcePMCen_US
dc.titleEpidermal growth factor receptor downregulation by small heterodimeric binding proteinsen_US
dc.typeArticleen_US
dc.identifier.citationHackel, B. J., J. R. Neil, F. M. White, and K. D. Wittrup. Epidermal Growth Factor Receptor Downregulation by Small Heterodimeric Binding Proteins. Protein Engineering Design and Selection 25, no. 2 (January 16, 2012): 47-57.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorHackel, Benjamin J.en_US
dc.contributor.mitauthorNeil, Jason Roberten_US
dc.contributor.mitauthorWhite, Forest M.en_US
dc.contributor.mitauthorWittrup, Karl Daneen_US
dc.relation.journalProtein Engineering Design and Selectionen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHackel, B. J.; Neil, J. R.; White, F. M.; Wittrup, K. D.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-1545-1651
dc.identifier.orcidhttps://orcid.org/0000-0003-2398-5896
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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