ABCA1 mRNA is translated

Stable Identifier
R-HSA-9618479
Type
Reaction [omitted]
Species
Homo sapiens
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The ATP-binding cassette sub-family A member 1 (ABCA1) mRNA is translated to yield ABCA1 protein.

Synthetic agonists of liver X-receptors (LXRα, NR1H3 and LXRβ, NR1H2) or cholesterol-loading significantly induced the expression of ABCA1 protein in mouse RAW 264.7 and human THP-1 macrophage cell lines (Beyea MM et al. 2007; Ku CS et al. 2012). Similar regulation of ABCA1 protein expression by NR1H2, 3 agonists was observed in human peripheral blood-derived monocytes (Mauerer R et al. 2009). Treatment of THP-1 macrophages with endogenous (25-hydroxycholesterol) or synthetic (T0901317) ligands of NR1H2,3 stimulated both transcriptional and posttranscriptional pathways to enhance ABCA1 expression (Ignatova ID et al. 2013). Further, partial inhibition of oxidosqualene:lanosterol cyclase (OSC) stimulated synthesis of the NR1H2,3 agonist 24(S),25-epoxycholesterol (24(S),25-epoxy) and enhanced ABCA1-mediated cholesterol efflux in THP-1 cells (Beyea MM et al. 2007). NR1H3 and NR1H2-induced expression of ABCA1 is thought to promote cellular cholesterol transfer to lipid-poor apolipoproteins such as ApoA1 and ApoE in the formation of nascent HDL particles (Ignatova ID et al. 2013; Vedhachalam C et al. 2007). Loss of ABCA1 in humans results in Tangier disease, a condition in which patients have extremely low levels of circulating HDL, massive accumulation of cholesterol in macrophages, and an increased risk for developing atherosclerosis (Rust S et al. 1999).

MicroRNAs miR-26 and miR-33 negatively regulate the translation of ABCA1 mRNA and thus repress the NR1H2, NR1H3-dependent cholesterol efflux from macrophages (Sun D et al. 2012; Rayner KJ et al. 2010). MicroRNA miR-144 also binds the ABCA1 3’UTR to prohibit translation and reduce ABCA1-mediated cholesterol efflux from hepatocytes (de Aguiar Vallim TQ et al. 2013)

Literature References
PubMed ID Title Journal Year
21187453 Constitutive activation of LXR in macrophages regulates metabolic and inflammatory gene expression: identification of ARL7 as a direct target

Hong, C, Walczak, R, Dhamko, H, Bradley, MN, Marathe, C, Boyadjian, R, Salazar, JV, Tontonoz, P

J. Lipid Res. 2011
17186944 Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol

Beyea, MM, Heslop, CL, Sawyez, CG, Edwards, JY, Markle, JG, Hegele, RA, Huff, MW

J. Biol. Chem. 2007
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