The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates
All proteins are subject to quality control processes during or soon after their synthesis, and these cellular quality control pathways play critical roles in maintaining homeostasis in the cell and in organism health. Protein quality control is particularly vital for those polypeptides that enter t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/8/1185 |
| _version_ | 1797524488858894336 |
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| author | Deepa Kumari Jeffrey L. Brodsky |
| author_facet | Deepa Kumari Jeffrey L. Brodsky |
| author_sort | Deepa Kumari |
| collection | DOAJ |
| description | All proteins are subject to quality control processes during or soon after their synthesis, and these cellular quality control pathways play critical roles in maintaining homeostasis in the cell and in organism health. Protein quality control is particularly vital for those polypeptides that enter the endoplasmic reticulum (ER). Approximately one-quarter to one-third of all proteins synthesized in eukaryotic cells access the ER because they are destined for transport to the extracellular space, because they represent integral membrane proteins, or because they reside within one of the many compartments of the secretory pathway. However, proteins that mature inefficiently are subject to ER-associated degradation (ERAD), a multi-step pathway involving the chaperone-mediated selection, ubiquitination, and extraction (or “retrotranslocation”) of protein substrates from the ER. Ultimately, these substrates are degraded by the cytosolic proteasome. Interestingly, there is an increasing number of native enzymes and metabolite and solute transporters that are also targeted for ERAD. While some of these proteins may transiently misfold, the ERAD pathway also provides a route to rapidly and quantitatively downregulate the levels and thus the activities of a variety of proteins that mature or reside in the ER. |
| first_indexed | 2024-03-10T08:58:08Z |
| format | Article |
| id | doaj.art-1a96bde198814e6b93502d78c76fff98 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T08:58:08Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-1a96bde198814e6b93502d78c76fff982023-11-22T06:56:04ZengMDPI AGBiomolecules2218-273X2021-08-01118118510.3390/biom11081185The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated SubstratesDeepa Kumari0Jeffrey L. Brodsky1Department of Biological Sciences, University of Pittsburgh, A320 Langley Hall, Fifth & Ruskin Ave, Pittsburgh, PA 15260, USADepartment of Biological Sciences, University of Pittsburgh, A320 Langley Hall, Fifth & Ruskin Ave, Pittsburgh, PA 15260, USAAll proteins are subject to quality control processes during or soon after their synthesis, and these cellular quality control pathways play critical roles in maintaining homeostasis in the cell and in organism health. Protein quality control is particularly vital for those polypeptides that enter the endoplasmic reticulum (ER). Approximately one-quarter to one-third of all proteins synthesized in eukaryotic cells access the ER because they are destined for transport to the extracellular space, because they represent integral membrane proteins, or because they reside within one of the many compartments of the secretory pathway. However, proteins that mature inefficiently are subject to ER-associated degradation (ERAD), a multi-step pathway involving the chaperone-mediated selection, ubiquitination, and extraction (or “retrotranslocation”) of protein substrates from the ER. Ultimately, these substrates are degraded by the cytosolic proteasome. Interestingly, there is an increasing number of native enzymes and metabolite and solute transporters that are also targeted for ERAD. While some of these proteins may transiently misfold, the ERAD pathway also provides a route to rapidly and quantitatively downregulate the levels and thus the activities of a variety of proteins that mature or reside in the ER.https://www.mdpi.com/2218-273X/11/8/1185ERADmolecular chaperonesubiquitinproteasomeprotein quality control |
| spellingShingle | Deepa Kumari Jeffrey L. Brodsky The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates Biomolecules ERAD molecular chaperones ubiquitin proteasome protein quality control |
| title | The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates |
| title_full | The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates |
| title_fullStr | The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates |
| title_full_unstemmed | The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates |
| title_short | The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates |
| title_sort | targeting of native proteins to the endoplasmic reticulum associated degradation erad pathway an expanding repertoire of regulated substrates |
| topic | ERAD molecular chaperones ubiquitin proteasome protein quality control |
| url | https://www.mdpi.com/2218-273X/11/8/1185 |
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