NR1H2,3 binds the CETP gene

Stable Identifier
R-HSA-9035133
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
Synonyms
LXR binds the CETP gene
ReviewStatus
5/5
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NR1H2,3 binds the CETP gene
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Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high density lipoprotein particles to triglyceride-rich lipoproteins for subsequent clearance by the liver. CETP expression can be transcriptionally activated by liver X receptors (LXRα (NR1H3) and LXRβ (NR1H2)) that belong to the nuclear receptor superfamily of ligand-activated transcription factors. Activation of NR1H2,3 induced expression via an LXR response element (LXRE) consisting of 2 hexanucleotide sequences separated by 4 intervening bases (an LXRE of the DR4 type) in the CETP promoter (Luo Y & Tall AR 2000), which may be more responsive to NR1H3 (LXRα) rather than NR1H2 (LXRβ) (Honzumi S et al. 2010). Treatment with T0901317, a synthetic agonist of NR1H2, 3, increased CETP mRNA levels in human liver carcinoma HepG2 cells by approximately 220%, while NR1H3 silencing markedly diminished the increased expression of CETP (Shimada A et al. 2016). It should be noted that CETP is not expressed in the mouse or rat (it is a pseudogene in these species, Hogarth CA et al. 2003), so studies of LXR-mediated regulation of CETP and its effects have been performed in human, hamster, and non-human primates (Groot PHE, et al. 2005).
Literature References
PubMed ID Title Journal Year
20494359 LXRalpha regulates human CETP expression in vitro and in transgenic mice

Honzumi, S, Shima, A, Hiroshima, A, Koieyama, T, Ubukata, N, Terasaka, N

Atherosclerosis 2010
26984517 Serum CETP status is independently associated with reduction rates in LDL-C in pitavastatin-treated diabetic patients and possible involvement of LXR in its association

Shimada, A, Kimura, H, Oida, K, Kanehara, H, Bando, Y, Sakamoto, S, Wakasugi, T, Saga, T, Ito, Y, Kamiyama, K, Mikami, D, Iwano, M, Hirano, T, Yoshida, H

Lipids Health Dis 2016
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Authored
Shamovsky, V  (2018-01-19)
Reviewed
D'Eustachio, P  (2018-12-29)
Cummins, CL  (2019-08-09)
Repa, JJ  (2019-08-09)
Created
Shamovsky, V  (2018-01-19)
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