Description
Title: An Expanding Menu of Regulated Substances: The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway
Abstract: All proteins go through quality control procedures either during or shortly after they are synthesized, and these cellular quality control pathways are essential for preserving cellular homeostasis and the wellbeing of the organism. Controlling the quality of proteins is crucial for polypeptides that enter the endoplasmic reticulum (ER). Because they are intended for transport to the extracellular space, because they are integral membrane proteins, or because they are located in one of the many compartments of the secretory pathway, roughly one-quarter to one-third of all proteins synthesized in eukaryotic cells enter the ER. ER-associated degradation (ERAD), a multi-step pathway involving chaperone-mediated selection, ubiquitination, and extraction (or “retrotranslocation”) of protein substrates from the ER, is instead a consequence of inefficient protein maturation. These substrates are ultimately broken down by the cytosolic proteasome. It’s interesting to note that ERAD is increasingly targeting native enzymes, metabolite transporters, and solute transporters. The ERAD pathway offers a way to quickly and quantitatively downregulate the levels and, consequently, the activities of a variety of proteins that mature or reside in the ER, even though some of these proteins may momentarily misfold.
Keywords: ERAD; molecular chaperones; ubiquitin; proteasome; protein quality control
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Biomolecules
Writer Experience: 20+ Years
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