A regulatory link between ER-associated protein degradation and the unfolded-protein response

• Published in: Nature cell biology Vol. 2; no. 7; pp. 379 - 384
• Main Authors: Sommer, Thomas, Friedlander, Ruth, Jarosch, Ernst, Urban, Jörg, Volkwein, Corinna
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2000
• Subjects: Carboxypeptidases - metabolism; Cathepsin A; Cell Division; Cellular proteins; Dithiothreitol - pharmacology; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Enzymes; Epistasis, Genetic; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene mutations; Genes, Fungal - genetics; Genes, Lethal - genetics; Half-Life; Kinases; Ligases - genetics; Ligases - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Molecular chaperones; Phenotype; Physiological aspects; Protein Conformation - drug effects; Protein Denaturation; Protein Folding; Protein-Serine-Threonine Kinases; Proteins; Proteins - genetics; Proteins - metabolism; Quantitative analysis; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; ubiquitin; ubiquitin-conjugating enzyme; Ubiquitin-Conjugating Enzymes; Ubiquitin-Protein Ligases; Up-Regulation - drug effects; Yeast
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/35017001

Ubiquitin conjugation during endoplasmic-reticulum-associated degradation (ERAD) depends on the activity of Ubc7. Here we show that Ubc1 acts as a further ubiquitin-conjugating enzyme in this pathway. Absence of both enzymes results in marked stabilization of an ERAD substrate and induction of the unfolded-protein response (UPR). Furthermore, basic ERAD activity is sufficient to eliminate unfolded proteins under normal conditions. However, when stress is applied, the UPR is required to increase ERAD activity. We thus demonstrate, for the first time, a regulatory loop between ERAD and the UPR, which is essential for normal growth of yeast cells.