title: Novel ubiquitin-dependent quality control in the endoplasmic reticulum.
abstract: Proteins of the endomembrane system undergo assisted folding in the endoplasmic reticulum (ER), then quality-control and, if misfolded, ER-associated degradation (ERAD). Recent findings on the biogenesis of a type-I membrane protein (an LRP6 mutant) lead us to hypothesize the existence of a novel mechanism promoting folding of membrane proteins from the cytosolic side of the ER. The proposed folding mechanism involves cycles of chaperone binding through mono-ubiquitylation and de-ubiquitylation, followed eventually by poly-ubiquitylation and ERAD. This suggests a novel dual role for ubiquitylation in the ER - dependent on the type of ubiquitin chains involved - in folding and in degradation, and highlights the potential importance of de-ubiquitylating enzymes.
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH 1015 Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Feldman
authors.forename: F Gisou
authors.initials: FG
authors.lastname: van der Goot
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D017510:Protein Folding; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin