{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:29:25Z","timestamp":1779258565224,"version":"3.51.4"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>ATP-binding cassette transporter A1 (ABCA1) exerts an atheroprotective action through the biogenesis of high-density lipoprotein in hepatocytes and prevents the formation of foam cells from macrophages. Controlling ABCA1 is a rational approach to improving atherosclerotic cardiovascular disease. Although much is known about the regulatory mechanism of ABCA1 synthesis, the molecular mechanism underpinning its degradation remains to be clearly described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      ABCA1 possesses potential sites of phosphorylation by serine\/threonine-protein kinase Pim-1 (Pim-1). Pim-1 depletion decreased the expression of cell surface\u2013resident ABCA1 (csABCA1) and apolipoprotein A-I\u2013mediated [\n                      <jats:sup>3<\/jats:sup>\n                      H]cholesterol efflux in the human hepatoma cell line HepG2, but not in peritoneal macrophages from mice. In vitro kinase assay, immunoprecipitation, and immunocytochemistry suggested phosphorylation of csABCA1 by the long form of Pim-1 (Pim-1L). Cell surface biotinylation indicated that Pim-1L inhibited lysosomal degradation of csABCA1 involving the liver X receptor \u03b2, which interacts with csABCA1 and thereby protects it from ubiquitination and subsequent lysosomal degradation. Cell surface coimmunoprecipitation with COS-1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that Pim-1L\u2013mediated phosphorylation of csABCA1 facilitated the interaction between csABCA1 and liver X receptor \u03b2 and thereby stabilized the csABCA1\u2013Pim-1L complex. Mice deficient in Pim-1 kinase activity showed lower expression of ABCA1 in liver plasma membranes and lower plasma high-density lipoprotein levels than control mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Pim-1L protects hepatic csABCA1 from lysosomal degradation by facilitating the physical interaction between csABCA1 and liver X receptor \u03b2 and subsequent stabilization of the csABCA1\u2013Pim-1L complex and thereby regulates the circulating level of high-density lipoprotein. Our findings may aid the development of high-density lipoprotein\u2013targeted therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.116.308472","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T22:59:32Z","timestamp":1477004372000},"page":"2304-2314","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Pim-1L Protects Cell Surface\u2013Resident ABCA1 From Lysosomal Degradation in Hepatocytes and Thereby Regulates Plasma High-Density Lipoprotein Level"],"prefix":"10.1161","volume":"36","author":[{"given":"Akira","family":"Katsube","sequence":"first","affiliation":[{"name":"From the Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisamitsu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"From the Laboratory of 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