NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease
Identifieur interne : 000100 ( Main/Exploration ); précédent : 000099; suivant : 000101NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease
Auteurs : Christian Bindesb Ll [Norvège] ; Aleksander Aas [Norvège] ; Margret Helga Ogmundsdottir [Islande] ; Serhiy Pankiv [Norvège] ; Trine Reine [Norvège] ; Roberto Zoncu [États-Unis] ; Anne Simonsen [Norvège]Source :
- Scientific Reports [ 2045-2322 ] ; 2020.
Abstract
Dysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Identification of the mechanisms involved in regulation of these processes are thus key to understand the pathology of coronary artery disease. Here, we identify the large and poorly characterized BEACH domain protein Neurobeachin-like (NBEAL) 1 as a Golgi- associated protein required for regulation of cholesterol metabolism.
Url:
DOI: 10.1038/s41598-020-61352-0
PubMed: 32161285
PubMed Central: 7066131
Affiliations:
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7878</institution-id><institution-id institution-id-type="GRID">grid.47840.3f</institution-id><institution>Department of Molecular and Cell Biology,</institution><institution>University of California, Berkeley,</institution></institution-wrap>Berkeley, CA 94720 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Berkeley</wicri:cityArea></affiliation></author><author><name sortKey="Simonsen, Anne" sort="Simonsen, Anne" uniqKey="Simonsen A" first="Anne" last="Simonsen">Anne Simonsen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8921</institution-id><institution-id institution-id-type="GRID">grid.5510.1</institution-id><institution>Department of Molecular Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine,</institution><institution>University of Oslo,</institution></institution-wrap>1112 Blindern, 0317 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>1112 Blindern, 0317 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Dysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Identification of the mechanisms involved in regulation of these processes are thus key to understand the pathology of coronary artery disease. Here, we identify the large and poorly characterized BEACH domain protein Neurobeachin-like (NBEAL) 1 as a Golgi- associated protein required for regulation of cholesterol metabolism. <italic>NBEAL1</italic> is most abundantly expressed in arteries. Genetic variants in <italic>NBEAL1</italic> are associated with decreased expression of <italic>NBEAL1</italic> in arteries and increased risk of coronary artery disease in humans. We show that NBEAL1 regulates cholesterol metabolism by modulating LDLR expression in a mechanism involving interaction with SCAP and PAQR3 and subsequent SREBP2-processing. Thus, low expression of <italic>NBEAL1</italic> may lead to increased risk of coronary artery disease by downregulation of LDLR levels.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jogl, G" uniqKey="Jogl G">G Jogl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gebauer, D" uniqKey="Gebauer D">D Gebauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holland, P" uniqKey="Holland P">P Holland</name></author><author><name sortKey="Torgersen, Ml" uniqKey="Torgersen M">ML Torgersen</name></author><author><name sortKey="Sandvig, K" uniqKey="Sandvig K">K Sandvig</name></author><author><name sortKey="Simonsen, A" uniqKey="Simonsen A">A Simonsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simonsen, A" uniqKey="Simonsen A">A Simonsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Ll C" first="Christian" last="Bindesb Ll">Christian Bindesb Ll</name></region><name sortKey="Aas, Aleksander" sort="Aas, Aleksander" uniqKey="Aas A" first="Aleksander" last="Aas">Aleksander Aas</name><name sortKey="Pankiv, Serhiy" sort="Pankiv, Serhiy" uniqKey="Pankiv S" first="Serhiy" last="Pankiv">Serhiy Pankiv</name><name sortKey="Reine, Trine" sort="Reine, Trine" uniqKey="Reine T" first="Trine" last="Reine">Trine Reine</name><name sortKey="Reine, Trine" sort="Reine, Trine" uniqKey="Reine T" first="Trine" last="Reine">Trine Reine</name><name sortKey="Simonsen, Anne" sort="Simonsen, Anne" uniqKey="Simonsen A" first="Anne" last="Simonsen">Anne Simonsen</name></country><country name="Islande"><noRegion><name sortKey="Ogmundsdottir, Margret Helga" sort="Ogmundsdottir, Margret Helga" uniqKey="Ogmundsdottir M" first="Margret Helga" last="Ogmundsdottir">Margret Helga Ogmundsdottir</name></noRegion></country><country name="États-Unis"><region name="Californie"><name sortKey="Zoncu, Roberto" sort="Zoncu, Roberto" uniqKey="Zoncu R" first="Roberto" last="Zoncu">Roberto Zoncu</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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