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Ubx2 links the Cdc48 complex to ER-associated protein degradation

Official URL:https://doi.org/10.1038/ncb1298
PubMed:View item in PubMed
Creators Name:Neuber, O. and Jarosch, E. and Volkwein, C. and Walter, J. and Sommer, T.
Journal Title:Nature Cell Biology
Journal Abbreviation:Nat Cell Biol
Volume:7
Number:10
Page Range:993-998
Date:18 September 2005
Keywords:Carrier Proteins, Cell Cycle Proteins, Cell Membrane, Cytosol, Endoplasmic Reticulum, Proteasome Endopeptidase Complex, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Abstract:Endoplasmic reticulum (ER)-associated protein degradation requires the dislocation of selected substrates from the ER to the cytosol for proteolysis via the ubiquitin -proteasome system. The AAA ATPase Cdc48 (known as p97 or VCP in mammals) has a crucial, but poorly understood role in this transport step. Here, we show that Ubx2 (Sel1) mediates interaction of the Cdc48 complex with the ER membrane-bound ubiquitin ligases Hrd1 (Der3) and Doa10. The membrane protein Ubx2 contains a UBX domain that interacts with Cdc48 and an additional UBA domain. Absence of Ubx2 abrogates breakdown of ER proteins but also that of a cytosolic protein, which is ubiquitinated by Doa10. Intriguingly, our results suggest that recruitment of Cdc48 by Ubx2 is essential for turnover of both ER and non-ER substrates, whereas the UBA domain of Ubx2 is specifically required for ER proteins only. Thus, a complex comprising the AAA ATPase, a ubiquitin ligase and the recruitment factor Ubx2 has a central role in ER-associated proteolysis.
ISSN:1465-7392
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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