ATP-binding transporters are transmembrane proteins that utilize the energy of adenosine triphosphate (ATP) hydrolysis to carry out certain biological processes including translocation of various substrates across membranes. They transport a variety of substrates across extra- and intracellular membranes, including metabolic products, lipids and sterols, and drugs. Proteins are classified as ATP-binding transporters based on the sequence and organization of their ATP-binding cassette (ABC) domain(s) [1].

ATP-binding transporters are regulated by different pathways. Nuclear receptor subfamily 1, group I, member 2 (PXR) and Retinoid X receptor, alpha (RXRA) are known transcriptional regulators of these transporters [2].

RXRA can associate with GATA binding protein 2 (GATA-2) [3] to activate the transcription of ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), which mediates export of Leukotriene C4 intracellular [4], [5], [6]. RXRA via GATA-2 also may regulate transcription of ATP-binding cassette, sub-family A (ABC1), member 3 (ABCA3) and ATP-binding cassette, sub-family C (CFTR/MRP), member 5 (ABCC5), and PXR activates expression of ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) [7], [8]. ABCA3, ABCC5 and ABCG2 promote drug export from the cytosol (e.g. Fluorouracil intracellular) [9], [10], [11].

In addition, RXRA via GATA-2 may regulate transcription of ATP-binding cassette, sub-family C (CFTR/MRP), member 1 (ABCC1) [12]. Also, a complex of PXR/RXR-alpha activates the transcription of ATP-binding cassette, sub-family C (CFTR/MRP), member 2 (ABCC2) [13]. ABCC1 and ABCC2 mediate bile acids export [14].

PXR/RXR-alpha complex and PXR itself activates the transcription of ATP-binding cassette, sub-family B (MDR/TAP), members 1 and 4 (MDR1 and MDR3), which are responsible for drug export, but also mediate Aldosterone and phospholipids export (e.g. 1,2-diacyl-glycerol 3-phosphocholine) [15], [16], [17], [18], [19].

Additionally, PXR activates the expression of ATP-binding cassette, sub-family C (CFTR/MRP), member 3 (MRP3), which is the transporter for Folic acid and also mediates export of Mono-conjugated bile acids [20], [21].

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