Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals
University of California, San Francisco · University of Michigan
Abstract
Cisplatin is a chemotherapeutic drug used to treat a variety of cancers. Both intrinsic and acquired resistance to cisplatin, as well as toxicity, limit its effectiveness. Molecular mechanisms that underlie cisplatin resistance are poorly understood. Here we demonstrate that deletion of the yeast CTR1 gene, which encodes a high-affinity copper transporter, results in increased cisplatin resistance and reduced intracellular accumulation of cisplatin. Copper, which causes degradation and internalization of Ctr1 protein (Ctr1p), enhances survival of wild-type yeast cells exposed to cisplatin and reduces cellular accumulation of the drug. Cisplatin also causes degradation and delocalization of Ctr1p and interferes…
Citation impact
- FWCI
- 15.58
- Percentile
- 100%
- References
- 39
Authors
4- SISeiko IshidaCorresponding
University of California, San Francisco, University of Michigan
- JLJaekwon Lee
University of California, San Francisco, University of Michigan
- DJDennis J. Thiele
University of California, San Francisco, University of Michigan
- IHIra Herskowitz
University of California, San Francisco, University of Michigan
Topics & keywords
- Cisplatin
- Transporter
- Yeast
- Toxicity
- Biology
- Pharmacology
- Saccharomyces cerevisiae
- Drug resistance
- Good health and well-being