Journal article : Review
Mechanisms of substrate processing during ER-associated protein degradation
- Abstract:
- Maintaining proteome integrity is essential for long-term viability of all organisms and is overseen by intrinsic quality control mechanisms. The secretory pathway of eukaryotes poses a challenge for such quality assurance as proteins destined for secretion enter the endoplasmic reticulum (ER) and become spatially segregated from the cytosolic machinery responsible for disposal of aberrant (misfolded or otherwise damaged) or superfluous polypeptides. The elegant solution provided by evolution is ER-membrane-bound ubiquitylation machinery that recognizes misfolded or surplus proteins or by-products of protein biosynthesis in the ER and delivers them to 26S proteasomes for degradation. ER-associated protein degradation (ERAD) collectively describes this specialized arm of protein quality control via the ubiquitin–proteasome system. But, instead of providing a single strategy to remove defective or unwanted proteins, ERAD represents a collection of independent processes that exhibit distinct yet overlapping selectivity for a wide range of substrates. Not surprisingly, ER-membrane-embedded ubiquitin ligases (ER-E3s) act as central hubs for each of these separate ERAD disposal routes. In these processes, ER-E3s cooperate with a plethora of specialized factors, coordinating recognition, transport and ubiquitylation of undesirable secretory, membrane and cytoplasmic proteins. In this Review, we focus on substrate processing during ERAD, highlighting common threads as well as differences between the many routes via ERAD.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Accepted manuscript, pdf, 3.0MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41580-023-00633-8
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Reviews Molecular Cell Biology More from this journal
- Volume:
- 24
- Issue:
- 11
- Pages:
- 777-796
- Publication date:
- 2023-08-01
- Acceptance date:
- 2023-06-20
- DOI:
- EISSN:
-
1471-0080
- ISSN:
-
1471-0072
- Language:
-
English
- Keywords:
- Subtype:
-
Review
- Pubs id:
-
1489067
- Local pid:
-
pubs:1489067
- Deposit date:
-
2023-07-02
Terms of use
- Copyright holder:
- Springer Nature Limited
- Copyright date:
- 2023
- Rights statement:
- Copyright © 2023, Springer Nature Limited
- Notes:
- This is the accepted manuscript version of the article. The final version is available online from Springer Nature at https://dx.doi.org/10.1038/s41580-023-00633-8
If you are the owner of this record, you can report an update to it here: Report update to this record