title: SLC28 genes and concentrative nucleoside transporter (CNT) proteins.
abstract: 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.
authors.affiliation: Facultat de Biologia, Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain. mpastor@ub.edu
authors.forename: M
authors.initials: M
authors.lastname: Pastor-Anglada
authors.forename: P
authors.initials: P
authors.lastname: Cano-Soldado
authors.forename: E
authors.initials: E
authors.lastname: Errasti-Murugarren
authors.forename: F J
authors.initials: FJ
authors.lastname: Casado
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000493:pharmacokinetics; D001692:Biological Transport; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D010597:Pharmacogenetics; D011684:Purine Nucleosides / Q000378:metabolism*; D011741:Pyrimidine Nucleosides / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D026901:Membrane Transport Proteins; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; C065171:cif nucleoside transporter