Letter abstract
Nature Cell Biology 7, 993 - 998 (2005)
Published online: 18 September 2005 | doi:10.1038/ncb1298
Ubx2 links the Cdc48 complex to ER-associated protein degradation
Oliver Neuber1, Ernst Jarosch1, Corinna Volkwein1, Jan Walter1,2 & Thomas Sommer1
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.
- Max-Delbrück Center for Molecular Medicine, Robert-Rössle Strasse 10, 13092 Berlin, Germany.
- Present address: Sergievsky Center, Columbia University, 630 W 168th Street, New York, NY 10032, USA.
Correspondence to: Thomas Sommer1 e-mail: tsommer@mdc-berlin.de
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