The role of Ctr1 and Ctr2 in mammalian copper homeostasis and platinum-based chemotherapy.
Copper (Cu) is an essential metal for growth and development that has the potential to be toxic if levels accumulate beyond the ability of cells to homeostatically balance uptake with detoxification. One system for Cu acquisition is the integral membrane Cu(+) transporter, Ctr1, which has been quite well characterized in terms of its function and physiology. The mammalian Ctr2 protein has been a conundrum for the copper field, as it is structurally closely related to the high affinity Cu transporter Ctr1, sharing important motifs for Cu transport activity. However, in contrast to mammalian Ctr1, Ctr2 fails to suppress the Cu-dependent growth phenotype of yeast cells defective in Cu(+) import, nor does it appreciably stimulate Cu acquisition when over-expressed in mammalian cells, underscoring important functional dissimilarities between the two proteins. Several roles for the mammalian Ctr2 have been suggested both in vitro and in vivo. Here, we summarize and discuss current insights into the Ctr2 protein and its interaction with Ctr1, its functions in mammalian Cu homeostasis and platinum-based chemotherapy.
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: helena.ohrvik@duke.edu.
Helena
H
Öhrvik
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Dennis J
DJ
Thiele
D020816:Amino Acid Motifs; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017671:Platinum Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000080083:SLC31 Proteins
D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D011994:Recombinant Proteins; D000080083:SLC31 Proteins; C490079:SLC31A1 protein, human; C524078:SLC31A2 protein, human; D003300:Copper
Copper trafficking; Copper transporter, Ctr; Platinum-based chemotherapy; Regulation; Structure