Feldman, M.van der Goot, F Gisou2010-07-292010-07-292010-07-29200910.1016/j.tcb.2009.05.005https://infoscience.epfl.ch/handle/20.500.14299/51924WOS:000269475300001Proteins 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.Proteasomal DegradationMolecular ChaperonesMembrane-Proteins26S ProteasomeLigaseChainsErGlycoproteinsEndocytosisCalnexintext::journal::journal article::review article