Novel ubiquitin-dependent quality control in the endoplasmic reticulum.
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.
Feldman
M
M
Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH 1015 Lausanne, Switzerland.
van der Goot
F Gisou
FG
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D017510:Protein Folding; D025801:Ubiquitin / Q000378:metabolism*
D025801:Ubiquitin