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	J. Biol. Chem. Nov (2007); 282(45):32665-75
The Hsp110 Molecular Chaperone Stabilizes Apolipoprotein B from Endoplasmic Reticulum-associated Degradation -ERAD--
Hrizo SL, Gusarova V, Habiel DM, Goeckeler JL, Fisher EA, Brodsky JL
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260-
Abstract: Apolipoprotein B -apoB- is the most abundant protein in low density lipoproteins and plays key roles in cholesterol homeostasis- The co-translational degradation of apoB is controlled by fatty acid levels in the endoplasmic reticulum -ER- and is mediated by the proteasome- To define the mechanism of apoB degradation, we employed a cell-free system in which proteasome-dependent degradation is recapitulated with yeast cytosol, and we developed an apoB yeast expression system- We discovered that a yeast Hsp110, Sse1p, associates with and stabilizes apoB, which contrasts with data indicating that select Hsp70s and Hsp90s facilitate apoB degradation- However, the Ssb Hsp70 chaperones have no effect on apoB turnover- To determine whether our results are relevant in mammalian cells, Hsp110 was overexpressed in hepatocytes, and enhanced apoB secretion was observed- This study indicates that chaperones within distinct complexes can play unique roles during ER-associated degradation -ERAD-, establishes a role for Sse1-Hsp110 in ERAD, and identifies Hsp110 as a target to lower cholesterol-
[PUBMED: 17823116]