Jump to main content
Jump to site search

Issue 3, 2014
Previous Article Next Article

Copper binding modulates the platination of human copper chaperone Atox1 by antitumor trans-platinum complexes

Author affiliations

Abstract

The transport system of platinum-based anticancer agents is crucial for drug sensitivity. Increasing evidence indicates that the copper transport system is also involved in the cellular influx and efflux of platinum drugs. The copper chaperone Atox1 has been shown to bind to cisplatin in vitro and in cells. Previous results reveal that copper binding promotes the reaction between Atox1 and cisplatin. Here, we have performed detailed solution NMR and ESI-MS experiments to investigate the effect of Cu(I) binding on the reactions of Atox1 with two antitumor active trans-platinum agents, trans-EE and trans-PtTz. Results indicate that, similar to the reaction of cisplatin, copper coordination also enhances the platination of Atox1 by two trans-platinum complexes, and platinum binds to the copper coordinating residues. However, copper binding promotes the trans-platinum transfer from Atox1 to dithiothreitol (DTT). This result is in contrast to the reaction of Atox1 with cisplatin, in which the presence of copper largely suppresses the platination of DTT. Additionally, both apo- and CuI-Atox1 react faster with trans-platinum complexes than with cisplatin, however, less protein aggregation is observed in the reaction of trans-platinum complexes. These results indicate that the roles of Atox1 in the regulation of cellular trafficking of platinum drugs are dependent on the coordination configurations.

Graphical abstract: Copper binding modulates the platination of human copper chaperone Atox1 by antitumor trans-platinum complexes

Back to tab navigation

Supplementary files

Publication details

The article was received on 15 Nov 2013, accepted on 06 Jan 2014 and first published on 07 Jan 2014


Article type: Paper
DOI: 10.1039/C3MT00338H
Author version
available:
Download author version (PDF)
Citation: Metallomics, 2014,6, 491-497

  •   Request permissions

    Copper binding modulates the platination of human copper chaperone Atox1 by antitumor trans-platinum complexes

    Z. Xi, W. Guo, C. Tian, F. Wang and Y. Liu, Metallomics, 2014, 6, 491
    DOI: 10.1039/C3MT00338H

Search articles by author

Spotlight

Advertisements