The BioGRID | PUBLICATION VIEW

	Nat. Cell Biol. Oct (2005); 7(10):999-1006
Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation-
Schuberth C, Buchberger A
Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18, 82152 Martinsried, Germany-
Abstract: Endoplasmic reticulum -ER--associated protein degradation -ERAD- is a quality control system that removes misfolded proteins from the ER- ERAD substrates are channelled from the ER via a proteinacious pore to the cytosolic ubiquitin-proteasome system - a process involving dedicated ubiquitin ligases and the chaperone-like AAA ATPase Cdc48 -also known as p97-- How the activities of these proteins are coupled remains unclear- Here we show that the UBX domain protein Ubx2 is an integral ER membrane protein that recruits Cdc48 to the ER- Moreover, Ubx2 mediates binding of Cdc48 to the ubiquitin ligases Hrd1 and Doa10, and to ERAD substrates- In addition, Ubx2 and Cdc48 interact with Der1 and Dfm1, yeast homologues of the putative dislocation pore protein Derlin-1 -refs 11-13-- Lack of Ubx2 causes defects in ERAD that are exacerbated under stress conditions- These findings are consistent with a model in which Ubx2 coordinates the assembly of a highly efficient ERAD machinery at the ER membrane-
[PUBMED: 16179952]