The BioGRID | PUBLICATION VIEW

	EMBO J. May (2006); 25(9):1827-35
The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment-
Gauss R, Sommer T, Jarosch E
Max-Delbruck Center for Molecular Medicine, Berlin, Germany-
Abstract: Misfolded proteins of the endoplasmic reticulum -ER- are targeted to the cytoplasm for proteasomal degradation- Key components of this process are ER membrane-bound ubiquitin ligases- These ligases associate with the cytoplasmic AAA-ATPase Cdc48p-p97, which is thought to support the release of malfolded proteins from the ER- Here, we characterize a yeast protein complex containing the ubiquitin ligase Hrd1p and the ER membrane proteins Hrd3p and Der1p- Hrd3p binds malfolded proteins in the ER lumen enabling their delivery to downstream components- Therefore, we propose that Hrd3p acts as a substrate recruitment factor for the Hrd1p ligase complex- Hrd3p function is also required for the association of Cdc48p with Hrd1p- Moreover, our data demonstrate that recruitment of Cdc48p depends on substrate processing by the Hrd1p ligase complex- Thus, the Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex-
[PUBMED: 16619026]