NR1H2,3 binds the PLTP gene

Stable Identifier
Reaction [binding]
Homo sapiens
LXR binds the PLTP gene
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Phospholipid transfer protein (PLTP) gene expression can be transcriptionally activated by liver X receptors (LXRα (NR1H3) and LXRβ (NR1H2)) that belong to the nuclear receptor superfamily (Mak PA et al. 2002; Cao G et al. 2002; Laffitte BA et al. 2003). NR1H2 and NR1H3 act as cellular sensors of sterol levels and are transcriptionally activated by oxidized forms of cholesterol, oxysterols (Janowski BA et al. 1996). Synthetic LXR agonists, T0901317 or GW3965, induced the expression of PLTP in various tissues of mice in a coordinate manner with known LXR target genes (Cao G et al. 2002; Laffitte BA et al. 2003). PLTP expression was also highly induced by LXR (NR1H2 and NR1H3) and retinoid X receptor (RXR) agonists in murine peritoneal and human THP-1 macrophages (Mak PA et al. 2002; Laffitte BA et al. 2003). The ability of synthetic and oxysterol ligands to regulate PLTP mRNA in macrophages and liver was lost in animals lacking both NR1H3 (LXRα) and NR1H2 (LXRβ), confirming the critical role of these receptors (Laffitte BA et al. 2003). Once activated, NR1H2 or 3 recognize an LXR response element (LXRE) sequence containing a variant direct-repeat-4 (DR4) motif in the promoter regions of target genes. The PLTP promoter contains a high-affinity LXRE that was found to bind NR1H3:RXR heterodimers in vitro, and was activated by NR1H3:RXR in transient-transfection studies (Mak PA et al. 2002; Laffitte BA et al. 2003).

In addition to NR1H2 or NR1H3, PLTP expression is regulated by other nuclear receptor RXR heterodimers, including peroxisome proliferator-activated receptor α (PPARα):RXR and farnesoid X receptor (FXR):RXR (Mak PA et al. 2002; Tu AY & Albers JJ 2001).

Literature References
PubMed ID Title Journal Year
12454263 Identification of PLTP as an LXR target gene and apoE as an FXR target gene reveals overlapping targets for the two nuclear receptors

Mak, PA, Kast-Woelbern, HR, Anisfeld, AM, Edwards, PA

J. Lipid Res. 2002
12612088 The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions

Laffitte, BA, Joseph, SB, Chen, M, Castrillo, A, Repa, JJ, Wilpitz, D, Mangelsdorf, D, Tontonoz, P

Mol. Cell. Biol. 2003
Cite Us!