Half transporter

TMD and NBF (Fig. 1). Therefore, these transporters are termed half transporter (in contrast to full transporter) however, to achieve functional activity they have to form hetero- or homodimers. 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis-... 

Brangi M, Litman T, Ciotti M, Nishiyama K, Kohlhagen G, Takimoto C et al. Camptothecin resistance role of the ATP-binding cassette (ABC), mitoxan-trone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res 1999 59(23) 5938—5946. 

Fetsch P, Abati A, Ross DD et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 2000 113(Pt 11) 2011-2021. 

Honjo Y, Morisaki K, Huff LM, Robey RW, Hung J, Dean M, Bates SE. Single-nucleotide polymorphism (SNP) analysis in the ABC half-transporter ABCG2 (MXR/BCRP/ABCP1). Cancer Biol Ther 2002 1 696-702. 

Bates SE, Robey R, Miyake K, et al. The role of half-transporters in multidrug resistance. J Bioenerg Biomembr 2001 33(6) 503-511. 

Efflux systems of major importance in the intestinal epithelium are P-glycoprotein (P-gp) (Mizuno et al. 2003), multidrug resistance-associated protein 2 (MRP2) (Jansen et al. 1993), and breast cancer resistance protein (BCRP) (Doyle et al. 1998, Doyle and Ross 2003). The latter is described as a half-transporter and possibly functions as a homodimer (Schinkel and Jonker 2003). Details on the molecular weight, structure, substrates, and expression of P-gp, MRP2, and BCRP are listed in Table 3.2. It needs to be mentioned that expression of these intestinal efflux transporter systems shows high... 

BCRP is an ABC half-transporter and is expressed at very high levels in the intestine, liver, kidney and blood-brain barrier. However, the identified list of substrates and/or inhibitors is limited yet Mitox-antrone, topotecan, doxorubicin, flavopiridol, SN-38, Lysotracker green, BBR 3390, BODIPY-Prazosin, Rhodamin 123. As inhibitors GF 120918 and fu-mitremorgin C were identified (Doyle et al. 1998 Litman et al. 2000). 

The third ABC protein believed to play a role in clinical MDR, ABCG2 (MXR/BCRP) is a half transporter [15,34], with a unique domain arrangement, where the ABC is located at the N-lerminus (Fig. 2). This protein performs an active extrusion of hydrophobic, positively charged molecules... 

Breast Cancer Resistance Protein (BCRP) BCRP is one of the newer ABC transport proteins to be examined. The transporter was first identified in drug-resistant breast cancer cells.165 Structurally, BCRP differs from both P-gp and MRP in that it is a half-transporter and requires the formation of a protein dimer for functional transporter activity.166 There is a great deal of substrate overlap between P-gp and BCRP.167 In addition to being overexpressed in various tumor cells, BCRP has been detected in normal tissues such as the placenta, small intestine, liver, and capillary and venous endothelial cells.156... 

Rocchi, E., Khodjakov, A., Volk, E.L., Yang, C.H., Litman, T., Bates, S.E. et al. (2000) The product of the ABC half transporter gene ABCG2 (BCRP/MXR/ ABCP) is expressed in the plasma membrane. Biochemical and Biophysical Research Communications, 271, 42-46. 

Robey, R.W., Medina-Perez, W.Y., Nishiyama, K., Lahusen, T, Miyake, K. Litman, T, Senderowicz, A.M.. Ross. D.D., and Bates, S.E. (2001) Overexpression of the ATP-binding cassette half-transporter, ABCG2 (MXR/BCRP/ABCPl), in flavopiridol-resistant human breast cancer cells. Clinical Cancer Research, 1, 145-152. 

BCRP is a recently identified ABC transporter, originally identified by its ability to confer drug resistance that is independent of other ABC transporters including Pgp. Because it contains a single N-terminal ATP binding cassette, BCRP is referred to as a half-transporter. Nevertheless, BCRP is present in various tissues including the intestine, liver, kidney, brain, and placenta. Like... 

---