S. Nishikawa et al., Molecular chaperones in the yeast endoplasmic reticulum maintain the solubility of proteins for retrotranslocation and degradation, J CELL BIOL, 153(5), 2001, pp. 1061-1069
Endoplasmic reticulum (ER)-associated degradation (ERAD) is the process by
which aberrant proteins in the ER lumen are exported back to the cytosol an
d degraded by the proteasome. Although ER molecular chaperones are required
for ERAD, their specific role(s) in this process have been ill defined. To
understand how one group of interacting lumenal chaperones facilitates ERA
D, the fates of pro-cr-factor and a mutant form of carboxypeptidase Y were
examined both in vivo and in vitro. We found that these ERAD substrates are
stabilized and aggregate in the ER at elevated temperatures when BiP, the
Lumenal Hsp70 molecular chaperone, is mutated, or when the genes encoding t
he J domain-containing proteins Jem1p and SCJ1 are deleted. In contrast, de
letion of JEM1 and SCJ1 had little effect on the ERAD of a membrane protein
. These results suggest that one role of the BiP, Jem1p, and Scj1p chaperon
es is to maintain lumenal ERAD substrates in a retrotranslocation-competent
state.