Ubx2 links the Cdc48 complex to ER-associated protein degradation

被引:235
作者
Neuber, O [1 ]
Jarosch, E [1 ]
Volkwein, C [1 ]
Walter, J [1 ]
Sommer, T [1 ]
机构
[1] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany
关键词
D O I
10.1038/ncb1298
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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收藏
页码:993 / U92
页数:7
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