Mechanism and components of endoplasmic reticulum-associated degradation
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TLDR
In the ERAD pathway, molecular chaperones and lectin-like proteins are involved in the identification of misfolded proteins, ER-resident reductases cleave disulfide bonds in these proteins to facilitate retrograde transport to the cytosol and AAA(+) adenosine triphosphatase withdraws them from the retrotranslocation channel to theCytosol where they are degraded by the ubiquitin/proteasome system.Abstract:
The folding of secretory and membrane proteins takes place in the endoplasmic reticulum (ER). The quality of the proteins folded in the ER is carefully monitored by an ER quality control mechanism that allows only correctly folded proteins to be transported to their final destination, and misfolded or unassembled proteins to be retained in the ER and subsequently degraded in a process termed 'ER-associated degradation' (ERAD). The ERAD pathway is conserved from yeast to mammals, and plays an essential role in the maintenance of ER homeostasis, as well as in the prevention of various diseases that arise from the accumulation of aberrant proteins in the ER. In the ERAD pathway, molecular chaperones and lectin-like proteins are involved in the identification of misfolded proteins, ER-resident reductases cleave disulfide bonds in these proteins to facilitate retrograde transport to the cytosol and AAA(+) adenosine triphosphatase withdraws them from the retrotranslocation channel to the cytosol where they are degraded by the ubiquitin/proteasome system. The possible mechanisms that underlie ERAD and the various factors involved in this process are discussed in this article.read more
Citations
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References
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Quality control in the endoplasmic reticulum
Lars Ellgaard,Ari Helenius +1 more
TL;DR: Recent progress is discussed in understanding the conformation-specific sorting of proteins at the level of ER retention and export, which is important for the fidelity of cellular functions.
Journal ArticleDOI
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Ari Helenius,Markus Aebi +1 more
TL;DR: From a process involved in cell wall synthesis in archaea and some bacteria, N-linked glycosylation has evolved into the most common covalent protein modification in eukaryotic cells.
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TL;DR: Results suggest that the demonstrated preferential transport of GSSG compared to GSH into the ER lumen may contribute to this redox compartmentation.
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One step at a time: endoplasmic reticulum-associated degradation
TL;DR: The current understanding of each step during ERAD, with emphasis on the factors that catalyse distinct activities is summarized, to highlight the importance of this pathway.
Journal ArticleDOI
The endoplasmic reticulum and the unfolded protein response.
TL;DR: The endoplasmic reticulum is the site where proteins enter the secretory pathway, and those processes that prevent accumulation of unfolded proteins in the ER lumen are highly regulated by an intracellular signaling pathway known as the unfolded protein response (UPR).
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