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http://purl.uniprot.org/citations/31597442http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31597442http://www.w3.org/2000/01/rdf-schema#comment"

Objective

A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride.

Conclusions

Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.119.312589"xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Luo J."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Wei J."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Hu A."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Fu Z.Y."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Lu X.F."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Song B.L."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Lu X.Y."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Ma Y.T."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Wang J.K."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Zhou Y.X."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Baituola G."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Meng Y.J."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/author"Adi D."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/pages"2468-2479"xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/title"IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation."xsd:string
http://purl.uniprot.org/citations/31597442http://purl.uniprot.org/core/volume"39"xsd:string
http://purl.uniprot.org/citations/31597442http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31597442
http://purl.uniprot.org/citations/31597442http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31597442
http://purl.uniprot.org/uniprot/#_B2RBG2-mappedCitation-31597442http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31597442
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