Glycoprotein folding and quality-control mechanisms in protein-folding diseases
Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to pri...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2014-03-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/3/331 |
| _version_ | 1818041559995645952 |
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| author | Sean P. Ferris Vamsi K. Kodali Randal J. Kaufman |
| author_facet | Sean P. Ferris Vamsi K. Kodali Randal J. Kaufman |
| author_sort | Sean P. Ferris |
| collection | DOAJ |
| description | Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC) system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER). A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes. |
| first_indexed | 2024-12-10T08:32:21Z |
| format | Article |
| id | doaj.art-4b945711aebd4166b65eb19727e4ed86 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-10T08:32:21Z |
| publishDate | 2014-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-4b945711aebd4166b65eb19727e4ed862022-12-22T01:56:04ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-03-017333134110.1242/dmm.014589014589Glycoprotein folding and quality-control mechanisms in protein-folding diseasesSean P. FerrisVamsi K. KodaliRandal J. KaufmanBiosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC) system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER). A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes.http://dmm.biologists.org/content/7/3/331N-glycosylationGlycoprotein foldingER quality controlER-associated degradationER export |
| spellingShingle | Sean P. Ferris Vamsi K. Kodali Randal J. Kaufman Glycoprotein folding and quality-control mechanisms in protein-folding diseases Disease Models & Mechanisms N-glycosylation Glycoprotein folding ER quality control ER-associated degradation ER export |
| title | Glycoprotein folding and quality-control mechanisms in protein-folding diseases |
| title_full | Glycoprotein folding and quality-control mechanisms in protein-folding diseases |
| title_fullStr | Glycoprotein folding and quality-control mechanisms in protein-folding diseases |
| title_full_unstemmed | Glycoprotein folding and quality-control mechanisms in protein-folding diseases |
| title_short | Glycoprotein folding and quality-control mechanisms in protein-folding diseases |
| title_sort | glycoprotein folding and quality control mechanisms in protein folding diseases |
| topic | N-glycosylation Glycoprotein folding ER quality control ER-associated degradation ER export |
| url | http://dmm.biologists.org/content/7/3/331 |
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