PMID: 9437001Mar 14, 1998Paper

Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins

Molecular Biology of the Cell
J BordalloD H Wolf

Abstract

We have studied components of the endoplasmic reticulum (ER) proofreading and degradation system in the yeast Saccharomyces cerevisiae. Using a der3-1 mutant defective in the degradation of a mutated lumenal protein, carboxypeptidase yscY (CPY*), a gene was cloned which encodes a 64-kDa protein of the ER membrane. Der3p was found to be identical with Hrd1p, a protein identified to be necessary for degradation of HMG-CoA reductase. Der3p contains five putative transmembrane domains and a long hydrophilic C-terminal tail containing a RING-H2 finger domain which is oriented to the ER lumen. Deletion of DER3 leads to an accumulation of CPY* inside the ER due to a complete block of its degradation. In addition, a DER3 null mutant allele suppresses the temperature-dependent growth phenotype of a mutant carrying the sec61-2 allele. This is accompanied by the stabilization of the Sec61-2 mutant protein. In contrast, overproduction of Der3p is lethal in a sec61-2 strain at the permissive temperature of 25 degrees C. A mutant Der3p lacking 114 amino acids of the lumenal tail including the RING-H2 finger domain is unable to mediate degradation of CPY* and Sec61-2p. We propose that Der3p acts prior to retrograde transport of ER membrane an...Continue Reading

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Citations

Nov 16, 2011·Applied Microbiology and Biotechnology·Hiroyuki MukaiyamaKaoru Takegawa
Jan 13, 2006·Molecular Genetics and Genomics : MGG·A BoisraméJ-M Beckerich
Oct 18, 2002·Current Opinion in Cell Biology·Randolph Y Hampton
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Dec 3, 2013·Nature Cell Biology·Martin MehnertErnst Jarosch
Jan 7, 2005·The EMBO Journal·Alexander G Shearer, Randolph Y Hampton
Aug 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Alexandra StolzDieter H Wolf
Oct 27, 2011·The Journal of Biological Chemistry·Patrick G NeedhamJeffrey L Brodsky
Sep 25, 2008·The Journal of Biological Chemistry·Meredith Boyle MetzgerSusan Michaelis
Apr 11, 2009·The Journal of Biological Chemistry·Sven M AlbertsDieter H Wolf
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