Expression of EEPD1 regulated by NR1H2 or NR1H3

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R-HSA-9035180
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Reaction [omitted]
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Homo sapiens
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The endonuclease-exonuclease-phosphatase family domain containing 1 (EEPD1/KIAA1706) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. EEPD1 was found to localize to the plasma membrane owing to the presence of a myristoylation site in its N terminus (Nelson JK et al. 2017). EEPD1 was identified as a direct transcriptional target of the sterol-responsive nuclear receptors, liver X receptors α (LXRα, NR1H3) and β (LXRβ, NR1H2) in murine bone marrow-derived macrophages and J774 macrophages and in human monocyte-like THP-1 cells (Nelson JK et al. 2017). Induction of EEPD1 by LXRs is tissue-specific and does not occur in HepG2 (liver) or C2C12 (muscle) cells (Nelson JK et al. 2017). Silencing expression of EEPD1 attenuated NR1H2,3 (LXRs)-stimulated apolipoprotein A-I (Apo A1)-dependent cholesterol efflux in THP1 and J774 cells (Nelson JK et al. 2017). Further, the level of cellular ATP-binding cassette transporter (ABCA1) content at the plasma membrane was reduced by 50% in both EEPD1-silenced macrophage cell lines (Nelson JK et al. 2017). ABCA1 is known to mediate the efflux of cellular cholesterol to lipid-free ApoA-I and thus initiates the biogenesis of high-density lipoprotein (HDL) (Reviewed in Phillips M.C. 2018). EEPD1 is thought to promote NR1H2,3-mediated cellular cholesterol efflux in macrophages post-transcriptionally by controlling cellular levels and activity of ABCA1 at the plasma membrane (Nelson JK et al. 2017).

Literature References
PubMed ID Title Journal Year
28082258 EEPD1 Is a Novel LXR Target Gene in Macrophages Which Regulates ABCA1 Abundance and Cholesterol Efflux

Nelson, JK, Koenis, DS, Scheij, S, Cook, EC, Moeton, M, Santos, A, Lobaccaro, JA, Baron, S, Zelcer, N

Arterioscler. Thromb. Vasc. Biol. 2017
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