dc.contributor.author | Antonopoulos, Aristotelis | |
dc.contributor.author | Haslam, Stuart M. | |
dc.contributor.author | Dell, Anne | |
dc.contributor.author | Dewal, Mahender | |
dc.contributor.author | DiChiara, Andrew Stephen | |
dc.contributor.author | Taylor, Rebecca J. | |
dc.contributor.author | Harmon, Chyleigh J. | |
dc.contributor.author | Shoulders, Matthew D. | |
dc.date.accessioned | 2017-01-24T19:08:31Z | |
dc.date.available | 2017-01-24T19:08:31Z | |
dc.date.issued | 2015-10 | |
dc.date.submitted | 2015-09 | |
dc.identifier.issn | 1074-5521 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/106600 | |
dc.description.abstract | The molecular architecture of the mature N-glycome is dynamic, with consequences for both normal and pathologic processes. Elucidating cellular mechanisms that modulate the N-linked glycome is, therefore, crucial. The unfolded protein response (UPR) is classically responsible for maintaining proteostasis in the secretory pathway by defining levels of chaperones and quality control proteins. Here, we employ chemical biology methods for UPR regulation to show that stress-independent activation of the UPR’s XBP1s transcription factor also induces a panel of N-glycan maturation-related enzymes. The downstream consequence is a distinctive shift toward specific hybrid and complex N-glycans on N-glycoproteins produced from XBP1s-activated cells, which we characterize by mass spectrometry. Pulse-chase studies attribute this shift specifically to altered N-glycan processing, rather than to changes in degradation or secretion rates. Our findings implicate XBP1s in a new role for N-glycoprotein biosynthesis, unveiling an important link between intracellular stress responses and the molecular architecture of extracellular N-glycoproteins. | en_US |
dc.description.sponsorship | Edward Mallinckrodt, Jr. Foundation (Faculty Scholar Award) | en_US |
dc.description.sponsorship | Mizutani Foundation for Glycoscience (Innovation Grant) | en_US |
dc.description.sponsorship | Singapore-MIT Alliance for Research and Technology (SMART) | en_US |
dc.description.sponsorship | Massachusetts Institute of Technology | en_US |
dc.description.sponsorship | National Institute of Environmental Health Sciences (Grant P30-ES002109) | en_US |
dc.description.sponsorship | National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grants 1R03AR067503 and F31AR067615) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.chembiol.2015.09.006 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Dewal, Mahender B. et al. “XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans.” Chemistry & Biology 22.10 (2015): 1301–1312. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.mitauthor | Dewal, Mahender | |
dc.contributor.mitauthor | DiChiara, Andrew Stephen | |
dc.contributor.mitauthor | Taylor, Rebecca J. | |
dc.contributor.mitauthor | Harmon, Chyleigh J. | |
dc.contributor.mitauthor | Shoulders, Matthew D. | |
dc.relation.journal | Chemistry and Biology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Dewal, Mahender B.; DiChiara, Andrew S.; Antonopoulos, Aristotelis; Taylor, Rebecca J.; Harmon, Chyleigh J.; Haslam, Stuart M.; Dell, Anne; Shoulders, Matthew D. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9438-0643 | |
dc.identifier.orcid | https://orcid.org/0000-0002-6511-3431 | |
mit.license | PUBLISHER_CC | en_US |