XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans
| Autor: | Matthew D. Shoulders, Rebecca J. Taylor, Anne Dell, Andrew S. DiChiara, Mahender B. Dewal, Chyleigh J. Harmon, Stuart M. Haslam, Aristotelis Antonopoulos |
|---|---|
| Přispěvatelé: | Massachusetts Institute of Technology. Department of Chemistry, Dewal, Mahender, DiChiara, Andrew Stephen, Taylor, Rebecca J., Harmon, Chyleigh J., Shoulders, Matthew D., Biotechnology and Biological Sciences Research Council (BBSRC) |
| Rok vydání: | 2015 |
| Předmět: |
X-Box Binding Protein 1
Clinical Biochemistry 0305 Organic Chemistry Biochemistry DISEASE PATHWAY 0302 clinical medicine Drug Discovery 0303 health sciences General Medicine Cell biology DNA-Binding Proteins Molecular Medicine Electrophoresis Polyacrylamide Gel Life Sciences & Biomedicine Intracellular Biochemistry & Molecular Biology XBP-1 ENDOPLASMIC-RETICULUM Chemical biology Regulatory Factor X Transcription Factors Biology Real-Time Polymerase Chain Reaction Article 03 medical and health sciences QUALITY-CONTROL Polysaccharides Humans Secretion Transcription factor Molecular Biology Secretory pathway 030304 developmental biology Pharmacology Science & Technology STABILITY GLYCOSYLATION Organic Chemistry RECOGNITION 0601 Biochemistry And Cell Biology Glycome 0304 Medicinal And Biomolecular Chemistry GLYCOPROTEINS Proteostasis HEK293 Cells Protein Biosynthesis Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization CELLS Unfolded protein response Unfolded Protein Response 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | PMC |
| ISSN: | 1879-1301 |
| Popis: | 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. Edward Mallinckrodt, Jr. Foundation (Faculty Scholar Award) Mizutani Foundation for Glycoscience (Innovation Grant) Singapore-MIT Alliance for Research and Technology (SMART) Massachusetts Institute of Technology National Institute of Environmental Health Sciences (Grant P30-ES002109) National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grants 1R03AR067503 and F31AR067615) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|