SLC28 genes and concentrative nucleoside transporter (CNT) proteins
- Xenobiotica. 2008 Jul;38(7-8):972-94. doi: 10.1080/00498250802069096.
- 1. Facultat de Biologia, Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain. [email protected]
The human concentrative nucleoside transporter (hCNT) protein family has three members, hCNT1, 2, and 3, encoded by SLC28A1, A2, and A3 genes, respectively. hCNT1 and hCNT2 translocate pyrimidine- and purine-nucleosides, respectively, by a sodium-dependent mechanism, whereas hCNT3 shows broad substrate selectivity and the unique ability of translocating nucleosides both in a sodium- and a proton-coupled manner. hCNT proteins are also responsible for the uptake of most nucleoside-derived Antiviral and Anticancer drugs. Thus, hCNTs are key pharmacological targets. This review focuses on several crucial aspects of hCNT biology and pharmacology: protein structure-function, structural determinants for transportability, pharmacogenetics of hCNT-encoding genes, role of hCNT proteins in nucleoside-based therapeutics, and finally hCNT physiology.