Cloning of a human nucleoside transporter implicated in the Cellular uptake of adenosine and chemotherapeutic drugs


In most mammalian Cells nucleoside uptake occurs primarily via broad-specificity, es (e, equilibrative; s, sensitive to NBMPR inhibition) transporters that are potentlyinhibited by nitrobenzylthioinosine (NBMPR)1. These transporters are essential for nucleotide synthesis by salvage pathways in hemopoietic and other Cells that lack de novo pathways and are the route of Cellular uptake for many cytotoxic nucleosides used in cancer and viral chemotherapy1. They play an important role in adenosinemediated regulation of many physiological processes, including neurotransmission and platelet aggregation, and are a target for coronary vasodilator drugs. We have previously reported the purification of the prototypic es transporter from human erythrocytes2 and have shown that this glycoprotein of apparent M, 55,000 is immunologically related to nucleoside transporters from several other species and tissues, including human placenta3,4. Here we report the isolation of a human placental cDNA encoding a 456-residue glycoprotein with functional characteristics typical of an es-type transporter. It is predicted to possess 11 membrane-spanning regions and is homologous to several proteins of unknown function in yeast, nematodes, plants and mammals. Because of its central role in the uptake both of adenosine and of chemotherapeutic nucleosides, study of this protein should not only provide insights into the physiological roles of nucleoside transport but also open the way to improved therapies.

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Griffiths, M., Beaumont, N., Yao, S. et al. Cloning of a human nucleoside transporter implicated in the Cellular uptake of adenosine and chemotherapeutic drugs. Nat Med 3, 89–93 (1997).

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