Redundant and Antagonistic Roles of XTP3B and OS9 in Decoding Glycan and Non-glycan Degrons in ER-Associated Degradation
| Autor: | Ron R. Kopito, Annemieke T. van der Goot, Dara Leto, Thomas A. Shaler, Margaret M.P. Pearce |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Folding Glycan Glycosylation Endoplasmic Reticulum Article Cell Line 03 medical and health sciences 0302 clinical medicine Polysaccharides Cell Line Tumor Lectins medicine Humans Molecular Biology Er associated degradation Secretory pathway Glycoproteins chemistry.chemical_classification biology Lectin Glycoproteinosis Endoplasmic Reticulum-Associated Degradation Cell Biology Processivity medicine.disease Neoplasm Proteins Cell biology carbohydrates (lipids) HEK293 Cells 030104 developmental biology chemistry Cell culture Protein Translocation Systems biology.protein K562 Cells Glycoprotein 030217 neurology & neurosurgery |
| Zdroj: | Molecular Cell. 70:516-530.e6 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2018.03.026 |
| Popis: | Summary Glycoproteins engaged in unproductive folding in the ER are marked for degradation by a signal generated by progressive demannosylation of substrate N-glycans that is decoded by ER lectins, but how the two lectins, OS9 and XTP3B, contribute to non-glycosylated protein triage is unknown. We generated cell lines with homozygous deletions of both lectins individually and in combination. We found that OS9 and XTP3B redundantly promote glycoprotein degradation and stabilize the SEL1L/HRD1 dislocon complex, that XTP3B profoundly inhibits the degradation of non-glycosylated proteins, and that OS9 antagonizes this inhibition. The relative expression of OS9 and XTP3B and the distribution of glycan and non-glycan degrons within the same protein contribute to the fidelity and processivity of glycoprotein triage and, therefore, determine the fates of newly synthesized proteins in the early secretory pathway. |
| Databáze: | OpenAIRE |
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