ERdj5 Is Required as a Disulfide Reductase for Degradation of Misfolded Proteins in the ER.
Ushioda, Ryo 1*; Hoseki, Jun 1,2*; Araki, Kazutaka 1*; Jansen, Gregor 3; Thomas, David Y. 3; Nagata, Kazuhiro 1,2+
[Report] Science. Follow the Money. 321(5888):569-572, July 25, 2008.

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Membrane and secretory proteins cotranslationally enter and are folded in the endoplasmic reticulum (ER). Misfolded or unassembled proteins are discarded by a process known as ER-associated degradation (ERAD), which involves their retrotranslocation into the cytosol. ERAD substrates frequently contain disulfide bonds that must be cleaved before their retrotranslocation. Here, we found that an ER-resident protein ERdj5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins, and accelerated ERAD through its physical and functional associations with EDEM (ER degradation-enhancing [alpha]-mannosidase-like protein) and an ER-resident chaperone BiP. Thus, ERdj5 is a member of a supramolecular ERAD complex that recognizes and unfolds misfolded proteins for their efficient retrotranslocation.

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