A Review: Molecular Mechanism of Regulation of ABCA1 Expression

Abstract

ATP-binding cassette subfamily A member 1 (ABCA1) protein plays an essential role in a variety of events, such as cholesterol and phospholipid efflux, nascent high-density lipoprotein (HDL) biosynthesis, phospholipid translocation. Thus, there has been much research activity aimed at understanding the molecular mechanisms of regulating ABCA1 expression. In this review, we first discuss ABCA1 structure, tissue distribution, cellular localization and trafficking, as well as its function. Furthermore, current understanding of the molecular mechanisms involved in the regulation of ABCA1 expression are summarized. ABCA1 transcriptional regulation is mediated by a very complicated system, including nuclear receptor systems, factors binding to other sites in the ABCA1 promoter, cytokines, hormones, growth factors, lipid metabolites, enzymes, and other messengers/factors/pathways. In addition, ABCA1 post-transcriptional regulation is mediated by microRNA, long noncoding RNA, RNA-binding proteins, proteases, fatty acids, PDZ proteins, signaling proteins, and other factors. Compared to the transcriptional regulation of ABCA1 which is well established, the post-transcriptional regulation of ABCA1 expression is poorly understood.

Is reverse cholesterol transport regulated by active cholesterol?

“… The expression of the reverse cholesterol transport proteins ( 25 , 41 , 50 ). The turnover of the reverse cholesterol transport proteins ( 85 , 131 ). The phosphorylation of the reverse cholesterol transport proteins ( 85 , 133 ).…”

“… The turnover of the reverse cholesterol transport proteins ( 85 , 131 ). The phosphorylation of the reverse cholesterol transport proteins ( 85 , 133 ). The distribution of the reverse cholesterol transport proteins between the plasma membrane and endosomes ( 49 , 116 ).…”

“…The principal role of ABCA1 is to remove excess cell cholesterol ( 7 , 25 , 50 , 84 , 85 ). Accordingly, cholesterol enrichment stimulates ABCA1 activity ( 2 , 82 , 86 ).…”

“…Active cholesterol could also impact the abundance and activity of ABCA1 and ABCG1 post-translationally ( 25 , 84 , 85 ). The cholesterol-binding sites on these proteins might be instrumental ( 55 , 129 , 130 ).…”

“…The cholesterol-binding sites on these proteins might be instrumental ( 55 , 129 , 130 ). In particular, ABCA1 and ABCG1 are turned over with half-times of a few hours ( 25 , 85 , 131 ). Inhibition of their proteolytic processing by excess cholesterol might be mediated by the active fraction.…”