ER-associated Degradation and Its Involvement in Human Disease: Insights from Yeast
Endoplasmic reticulum-associated protein degradation (ERAD) is a cellular process that targets short-lived resident proteins and aberrant secretory proteins to the proteasome for degradation. ERAD is essential for maintaining the homeostasis of the secretory pathway, as the retention of misfolded proteins in the ER can lead to several diseases. The budding yeast Saccharomyces cerevisiae has been used as a model organism for dissecting the molecular components of the ERAD pathway. This review describes the multi-subunit protein machineries in the ER membrane that are involved in the recognition of misfolded proteins, their ubiquitylation, and their retro-translocation to the cytosol and delivery to the proteasome. Most of the yeast components are conserved in humans and the analysis of the function in ERAD of the yeast counterparts has been crucial in elucidating the mechanisms responsible for human disorders.
KeywordsEndoplasmic Reticulum Amyotrophic Lateral Sclerosis Endoplasmic Reticulum Stress Unfold Protein Response Misfolded Protein
We apologize to those whose work we were unable to cite due to space constraints. N. C is supported by a grant from the Fonds pour la formation à la Recherche dans l’Industrie et dans l’Agriculture (F.R.I.A.).
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