Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step.

ABSTRACT: Proteasomes mediate the regulated degradation of Insig-1, a membrane protein of the endoplasmic reticulum (ER) that plays a crucial role in lipid metabolism. We showed previously that sterols inhibit this degradation by blocking ubiquitination of Insig-1. Here we show that unsaturated fatty acids stabilize Insig-1 without affecting its ubiquitination. Instead unsaturated fatty acids inhibit extraction of ubiquitinated Insig-1 from membranes, a process known to be mediated by valosin-containing protein and necessary for ER-associated degradation. Valosin-containing protein is recruited to Insig-1 through the action of another protein, Ubxd8. Unsaturated fatty acids block the binding between Ubxd8 and Insig-1, thereby abrogating the membrane extraction of Insig-1. Unsaturated fatty acid-medi

SUBMITTER: Lee JN 

PROVIDER: S-EPMC2586246 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature