Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e
ER-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated posttranscriptionally and independently of the unfolded protein re...
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| Format: | Article |
| Language: | English |
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Elsevier BV
2019
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| Online Access: | https://hdl.handle.net/1721.1/121371 |
| _version_ | 1826211985009672192 |
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| author | Hagiwara, Masatoshi Ling, Jingjing Koenig, Paul-Albert Ploegh, Hidde L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hagiwara, Masatoshi Ling, Jingjing Koenig, Paul-Albert Ploegh, Hidde L. |
| author_sort | Hagiwara, Masatoshi |
| collection | MIT |
| description | ER-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated posttranscriptionally and independently of the unfolded protein response by adjusting the endogenous levels of EDEM1, OS-9, and SEL1L (ERAD enhancers). Functional UBC6e requires its precise location in the ER to form a supramolecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e's enzymatic activity. Ablation of UBC6e causes upregulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowly in vitro and in vivo. The levels of proteins that comprise the ERAD machinery are thus carefully tuned and adjusted to prevailing needs. |
| first_indexed | 2024-09-23T15:14:31Z |
| format | Article |
| id | mit-1721.1/121371 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:14:31Z |
| publishDate | 2019 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1213712022-10-02T01:36:22Z Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e Hagiwara, Masatoshi Ling, Jingjing Koenig, Paul-Albert Ploegh, Hidde L. Massachusetts Institute of Technology. Department of Biology ER-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated posttranscriptionally and independently of the unfolded protein response by adjusting the endogenous levels of EDEM1, OS-9, and SEL1L (ERAD enhancers). Functional UBC6e requires its precise location in the ER to form a supramolecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e's enzymatic activity. Ablation of UBC6e causes upregulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowly in vitro and in vivo. The levels of proteins that comprise the ERAD machinery are thus carefully tuned and adjusted to prevailing needs. 2019-06-20T15:28:45Z 2019-06-20T15:28:45Z 2016-08 2016-06 2019-06-17T23:12:59Z Article http://purl.org/eprint/type/JournalArticle 1097-2765 1097-4164 https://hdl.handle.net/1721.1/121371 Hagiwara, Masatoshi et al. "Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e." Molecular Cell 63, 5 (September 2016): 753-767 © 2016 Elsevier Inc en http://dx.doi.org/10.1016/J.MOLCEL.2016.07.014 Molecular Cell Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Hagiwara, Masatoshi Ling, Jingjing Koenig, Paul-Albert Ploegh, Hidde L. Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e |
| title | Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e |
| title_full | Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e |
| title_fullStr | Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e |
| title_full_unstemmed | Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e |
| title_short | Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e |
| title_sort | posttranscriptional regulation of glycoprotein quality control in the endoplasmic reticulum is controlled by the e2 ub conjugating enzyme ubc6e |
| url | https://hdl.handle.net/1721.1/121371 |
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