dc.contributor.author | Dvela-Levitt, Moran | en |
dc.contributor.author | Kost-Alimova, Maria | en |
dc.contributor.author | Emani, Maheswarareddy | en |
dc.contributor.author | Kohnert, Eva | en |
dc.contributor.author | Thompson, Rebecca | en |
dc.contributor.author | Sidhom, Eriene-Heidi | en |
dc.contributor.author | Rivadeneira, Ana | en |
dc.contributor.author | Sahakian, Nareh | en |
dc.contributor.author | Roignot, Julie | en |
dc.contributor.author | Papagregoriou, Gregory | en |
dc.contributor.author | Montesinos, Monica S. | en |
dc.contributor.author | Clark, Abbe R. | en |
dc.contributor.author | McKinney, David | en |
dc.contributor.author | Gutierrez, Juan | en |
dc.contributor.author | Roth, Mark | en |
dc.contributor.author | Ronco, Lucienne | en |
dc.contributor.author | Elonga, Esther | en |
dc.contributor.author | Carter, Todd A. | en |
dc.contributor.author | Gnirke, Andreas | en |
dc.contributor.author | Melanson, Michelle | en |
dc.contributor.author | Hartland, Kate | en |
dc.contributor.author | Wieder, Nicolas | en |
dc.contributor.author | Hsu, Jane C.-H. | en |
dc.contributor.author | Deltas, Constantinos | en |
dc.contributor.author | Hughey, Rebecca | en |
dc.contributor.author | Bleyer, Anthony J. | en |
dc.contributor.author | Kmoch, Stanislav | en |
dc.contributor.author | Živná, Martina | en |
dc.contributor.author | Barešova, Veronika | en |
dc.contributor.author | Kota, Savithri | en |
dc.contributor.author | Schlondorff, Johannes | en |
dc.contributor.author | Heiman, Myriam | en |
dc.contributor.author | Alper, Seth L. | en |
dc.contributor.author | Wagner, Florence | en |
dc.contributor.author | Weins, Astrid | en |
dc.contributor.author | Golub, Todd R. | en |
dc.contributor.author | Lander, Eric S. | en |
dc.contributor.author | Greka, Anna | en |
dc.creator | Dvela-Levitt, Moran | en |
dc.creator | Kost-Alimova, Maria | en |
dc.creator | Emani, Maheswarareddy | en |
dc.creator | Kohnert, Eva | en |
dc.creator | Thompson, Rebecca | en |
dc.creator | Sidhom, Eriene-Heidi | en |
dc.creator | Rivadeneira, Ana | en |
dc.creator | Sahakian, Nareh | en |
dc.creator | Roignot, Julie | en |
dc.creator | Papagregoriou, Gregory | en |
dc.creator | Montesinos, Monica S. | en |
dc.creator | Clark, Abbe R. | en |
dc.creator | McKinney, David | en |
dc.creator | Gutierrez, Juan | en |
dc.creator | Roth, Mark | en |
dc.creator | Ronco, Lucienne | en |
dc.creator | Elonga, Esther | en |
dc.creator | Carter, Todd A. | en |
dc.creator | Gnirke, Andreas | en |
dc.creator | Melanson, Michelle | en |
dc.creator | Hartland, Kate | en |
dc.creator | Wieder, Nicolas | en |
dc.creator | Hsu, Jane C.-H. | en |
dc.creator | Deltas, Constantinos | en |
dc.creator | Hughey, Rebecca | en |
dc.creator | Bleyer, Anthony J. | en |
dc.creator | Kmoch, Stanislav | en |
dc.creator | Živná, Martina | en |
dc.creator | Barešova, Veronika | en |
dc.creator | Kota, Savithri | en |
dc.creator | Schlondorff, Johannes | en |
dc.creator | Heiman, Myriam | en |
dc.creator | Alper, Seth L. | en |
dc.creator | Wagner, Florence | en |
dc.creator | Weins, Astrid | en |
dc.creator | Golub, Todd R. | en |
dc.creator | Lander, Eric S. | en |
dc.creator | Greka, Anna | en |
dc.date.accessioned | 2021-01-22T09:29:00Z | |
dc.date.available | 2021-01-22T09:29:00Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 1097-4172 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/61939 | |
dc.description.abstract | Intracellular accumulation of misfolded proteins causes toxic proteinopathies, diseases without targeted therapies. Mucin 1 kidney disease (MKD) results from a frameshift mutation in the MUC1 gene (MUC1-fs). Here, we show that MKD is a toxic proteinopathy. Intracellular MUC1-fs accumulation activated the ATF6 unfolded protein response (UPR) branch. We identified BRD4780, a small molecule that clears MUC1-fs from patient cells, from kidneys of knockin mice and from patient kidney organoids. MUC1-fs is trapped in TMED9 cargo receptor-containing vesicles of the early secretory pathway. BRD4780 binds TMED9, releases MUC1-fs, and re-routes it for lysosomal degradation, an effect phenocopied by TMED9 deletion. Our findings reveal BRD4780 as a promising lead for the treatment of MKD and other toxic proteinopathies. Generally, we elucidate a novel mechanism for the entrapment of misfolded proteins by cargo receptors and a strategy for their release and anterograde trafficking to the lysosome. | en |
dc.language.iso | eng | en |
dc.source | Cell | en |
dc.source.uri | http://www.ncbi.nlm.nih.gov/pubmed/31348885 | |
dc.title | Small Molecule Targets TMED9 and Promotes Lysosomal Degradation to Reverse Proteinopathy | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1016/j.cell.2019.07.002 | |
dc.description.volume | 178 | |
dc.description.issue | 3 | |
dc.description.startingpage | 521 | |
dc.description.endingpage | 5.35E+025 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Βιολογικών Επιστημών / Department of Biological Sciences | |
dc.type.uhtype | Article | en |
dc.source.abbreviation | Cell | en |
dc.contributor.orcid | Deltas, Constantinos [0000-0001-5549-9169] | |
dc.gnosis.orcid | 0000-0001-5549-9169 | |