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http://purl.uniprot.org/citations/19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19815544http://www.w3.org/2000/01/rdf-schema#comment"Polytopic membrane proteins subjected to endoplasmic reticulum (ER)-associated degradation are extracted from membranes and targeted to proteasomes for destruction. The extraction mechanism is poorly understood. One polytopic ER protein subjected to ER-associated degradation is Insig-1, a negative regulator of cholesterol synthesis. Insig-1 is rapidly degraded by proteasomes when cells are depleted of cholesterol, and its degradation is inhibited when sterols accumulate in cells. Insig-2, a functional homologue of Insig-1, is degraded slowly, and its degradation is not regulated by sterols. Here, we report that a single amino acid substitution in Insig-2, Insig-2(L210A), causes Insig-2 to be degraded in an accelerated and sterol-regulated manner similar to Insig-1. In seeking an explanation for the accelerated degradation, we found that proteasomes bind to wild type Insig-1 and mutant Insig-2(L210A) but not to wild type Insig-2, whereas the proteins are still embedded in cell membranes. This binding depends on at least two factors, ubiquitination of Insig and association with the ATPase p97/VCP complex. These data suggest that p97 recruits proteasomes to polytopic ER proteins even before they are extracted from membranes."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m109.044875"xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/author"Ye J."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/author"Ikeda Y."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/author"Brown M.S."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/author"Goldstein J.L."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/author"Lee J.N."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/author"Demartino G.N."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/pages"34889-34900"xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/title"Regulated endoplasmic reticulum-associated degradation of a polytopic protein: p97 recruits proteasomes to Insig-1 before extraction from membranes."xsd:string
http://purl.uniprot.org/citations/19815544http://purl.uniprot.org/core/volume"284"xsd:string
http://purl.uniprot.org/citations/19815544http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19815544
http://purl.uniprot.org/citations/19815544http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19815544
http://purl.uniprot.org/uniprot/#_A4D2M9-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_A0A2Z2EKN2-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_B4DM22-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_F5H6P3-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_Q13200-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_Q13041-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_O15503-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_Q59EG8-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544
http://purl.uniprot.org/uniprot/#_Q9NSM5-mappedCitation-19815544http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19815544