Journal ArticleDOI
Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48.
Ernst Jarosch,Christof Taxis,Corinna Volkwein,Javier Bordallo,Daniel Finley,Dieter H. Wolf,Thomas Sommer +6 more
TLDR
It is shown that short ubiquitin chains synthesized on proteolytic substrates are not sufficient to complete dislocation; the size of the chain seems to be a critical determinant.Abstract:
Endoplasmic reticulum (ER)-associated protein degradation by the ubiquitin-proteasome system requires the dislocation of substrates from the ER into the cytosol. It has been speculated that a functional ubiquitin proteasome pathway is not only essential for proteolysis, but also for the preceding export step. Here, we show that short ubiquitin chains synthesized on proteolytic substrates are not sufficient to complete dislocation; the size of the chain seems to be a critical determinant. Moreover, our results suggest that the AAA proteins of the 26S proteasome are not directly involved in substrate export. Instead, a related AAA complex Cdc48, is required for ER-associated protein degradation upstream of the proteasome.read more
Citations
More filters
Journal ArticleDOI
One step at a time: endoplasmic reticulum-associated degradation
TL;DR: The current understanding of each step during ERAD, with emphasis on the factors that catalyse distinct activities is summarized, to highlight the importance of this pathway.
Journal ArticleDOI
ERAD: the long road to destruction
TL;DR: Advances in various aspects of ERAD are summarized and new findings on how substrate dislocation is achieved are discussed, to help clarify the spatial separation between substrate selection and degradation in ERAD.
Journal ArticleDOI
A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
TL;DR: A p97-interacting membrane protein complex in the mammalian ER that links elimination of misfolded proteins from the endoplasmic reticulum by retro-translocation and its subsequent movement through the membrane by the cytosolic p97 ATPase is identified.
Journal ArticleDOI
A membrane protein required for dislocation of misfolded proteins from the ER.
TL;DR: It is shown that US11 uses its transmembrane domain to recruit class I MHC products to a human homologue of yeast Der1p, a protein essential for the degradation of a subset of misfolded ER proteins.
Journal ArticleDOI
Retro-translocation of proteins from the endoplasmic reticulum into the cytosol
TL;DR: The mechanism of retro-translocation is still mysterious, but several aspects of this process are now being unravelled.
References
More filters
Journal ArticleDOI
Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae
Mark S. Longtine,Amos Mckenzie,Douglas J. Demarini,Nirav Shah,Achim Wach,Arndt Brachat,Peter Philippsen,John R. Pringle +7 more
TL;DR: A new set of plasmids that serve as templates for the PCR synthesis of fragments that allow a variety of gene modifications that should further facilitate the rapid analysis of gene function in S. cerevisiae.
Journal ArticleDOI
Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation
Kevin J. Travers,Christopher K Patil,Lisa Wodicka,David J. Lockhart,Jonathan S. Weissman,Peter Walter +5 more
TL;DR: The unfolded protein response and ERAD are dynamic responses required for the coordinated disposal of misfolded proteins even in the absence of acute stress.
Journal ArticleDOI
Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction.
Emmanuel J. H. J. Wiertz,Domenico Tortorella,Matthew Bogyo,Joyce Yu,Walther Mothes,Thomas R. Jones,Tom A. Rapoport,Hidde L. Ploegh +7 more
TL;DR: The human cytomegalovirus genome encodes proteins that trigger destruction of newly synthesized major histocompatibility complex (MHC) class I molecules, which involves the Sec6l complex, in what appears to be a reversal of the reaction by which it translocates nascent chains into the endoplasmic reticulum.
Journal ArticleDOI
A proteolytic pathway that recognizes ubiquitin as a degradation signal.
TL;DR: It is shown that a Lys Arg conversion at either position 29 or position 48 in the fusion's Ub moiety greatly reduces ubiquitination and degradation of Ub fusions to β-galactosidase and that structurally different multi-Ub chains have distinct functions in Ub-dependent protein degradation.
Journal ArticleDOI
A Yeast Mutant Showing Diagnostic Markers of Early and Late Apoptosis
TL;DR: A Saccharomyces cerevisiae mutant in cell division cycle gene CDC48 shows typical markers of apoptosis: membrane staining with annexin V, indicating an exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane; intense staining, using the terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling method, indicating DNA fragmentation; and chromatin condensation and fragmentation.