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ER-associated degradation in protein quality control and cellular regulation
Abstract
The ER-associated degradation (ERAD) pathway directs ubiquitin-mediated degradation of a variety of ER-associated misfolded and normal proteins. Recent studies have delineated the molecular machinery responsible for protein ubiquitination and highlighted mechanistic questions surrounding the recognition, extraction and proteasomal destruction of the diverse array of ERAD substrates. Consideration of separate lines of work on this versatile pathway now indicate that despite its central role as an avenue of cellular quality control, ERAD is also harnessed for feedback regulation of sterol synthesis, and most likely numerous other cellular processes. These studies give ERAD a larger role in cellular function, and imply that cellular quality-control pathways could be widely employed in both natural and pharmaceutical control of individual proteins.
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ER retention of the complex of PCSK9 with APLP2, sAPLP2, and sortilin likely leads to their degradation within the ERAD system.
“However, because PCSK9-KDEL is also able to degrade APLP2, sAPLP2, and sortilin (Fig. 5), this suggests that ER retention of the complex of PCSK9 with these proteins likely leads to their degradation within the ERAD system (50).”
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Friedlander, R., Jarosch, E., Urban, J., Volkwein, C., & Sommer, T. (2000) · Nature Cell Biology · doi:10.1038/35017001 · Cited by 474
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Metadata
- Authors
- Hampton, R. Y.
- Venue
- Current Opinion in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 14
- Issue
- 4
- Pages
- 476-482
- ISSN
- 0955-0674
- Cited by
- 415
- References
- 2
- Language
- en
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