Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen
Degrons are minimal protein features that are sufficient to target proteins for degradation. In most cases, degrons allow recognition by components of the cytosolic ubiquitin proteasome system. Currently, all of the identified degrons only function within the cytosol. Using Saccharomyces cerevisiae,...
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| Format: | Article |
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eLife Sciences Publications Ltd
2024-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89606 |
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| author | Rachel Sharninghausen Jiwon Hwang Devon D Dennison Ryan D Baldridge |
| author_facet | Rachel Sharninghausen Jiwon Hwang Devon D Dennison Ryan D Baldridge |
| author_sort | Rachel Sharninghausen |
| collection | DOAJ |
| description | Degrons are minimal protein features that are sufficient to target proteins for degradation. In most cases, degrons allow recognition by components of the cytosolic ubiquitin proteasome system. Currently, all of the identified degrons only function within the cytosol. Using Saccharomyces cerevisiae, we identified the first short linear sequences that function as degrons from the endoplasmic reticulum (ER) lumen. We show that when these degrons are transferred to proteins, they facilitate proteasomal degradation through the endoplasmic reticulum associated degradation (ERAD) system. These degrons enable degradation of both luminal and integral membrane ER proteins, expanding the types of proteins that can be targeted for degradation in budding yeast and mammalian tissue culture. This discovery provides a framework to target proteins for degradation from the previously unreachable ER lumen and builds toward therapeutic approaches that exploit the highly conserved ERAD system. |
| format | Article |
| id | doaj-art-c4f8fa13f6084e7cbcc314c713cdce20 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-c4f8fa13f6084e7cbcc314c713cdce202025-08-20T02:14:53ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011210.7554/eLife.89606Identification of ERAD-dependent degrons for the endoplasmic reticulum lumenRachel Sharninghausen0Jiwon Hwang1Devon D Dennison2Ryan D Baldridge3https://orcid.org/0000-0001-7158-7812Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United StatesDepartment of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United StatesCellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, United StatesDepartment of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States; Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, United StatesDegrons are minimal protein features that are sufficient to target proteins for degradation. In most cases, degrons allow recognition by components of the cytosolic ubiquitin proteasome system. Currently, all of the identified degrons only function within the cytosol. Using Saccharomyces cerevisiae, we identified the first short linear sequences that function as degrons from the endoplasmic reticulum (ER) lumen. We show that when these degrons are transferred to proteins, they facilitate proteasomal degradation through the endoplasmic reticulum associated degradation (ERAD) system. These degrons enable degradation of both luminal and integral membrane ER proteins, expanding the types of proteins that can be targeted for degradation in budding yeast and mammalian tissue culture. This discovery provides a framework to target proteins for degradation from the previously unreachable ER lumen and builds toward therapeutic approaches that exploit the highly conserved ERAD system.https://elifesciences.org/articles/89606degronsprotein degradationendoplasmic reticulum associated degradationERAD |
| spellingShingle | Rachel Sharninghausen Jiwon Hwang Devon D Dennison Ryan D Baldridge Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen eLife degrons protein degradation endoplasmic reticulum associated degradation ERAD |
| title | Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen |
| title_full | Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen |
| title_fullStr | Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen |
| title_full_unstemmed | Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen |
| title_short | Identification of ERAD-dependent degrons for the endoplasmic reticulum lumen |
| title_sort | identification of erad dependent degrons for the endoplasmic reticulum lumen |
| topic | degrons protein degradation endoplasmic reticulum associated degradation ERAD |
| url | https://elifesciences.org/articles/89606 |
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