Interaction between the Anticancer Drug Cisplatin and the Copper Chaperone Atox1 in Human Melanoma Cells

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Interaction Between Anticancer Drug Cisplatin and Copper Chaperone Atox1 in Human Melanoma Cells

Postprint This is the accepted version of a paper published in Protein peptide letters. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Interaction between anticancer drug Cisplatin and copper chaperone Atox1 in human melanoma cells. Protein peptide letters Access to the published version may require subscription. Cisplatin (Ci...

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Copper binding promotes the interaction of cisplatin with human copper chaperone Atox1.

Cu(I) binding promotes the platination of Atox1, although cisplatin binds to the copper coordination sites. In addition, Cu(I) binding enhances the competition of Atox1 with DTT in the reaction of cisplatin. These results indicate that cuprous ions could regulate the cellular trafficking of cisplatin.

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Interaction of cisplatin and analogue Pt(en)Cl2 with the copper metallo-chaperone Atox1.

The human metallo-chaperone protein Atox1 features a high affinity Cu(I) binding site Cys(12)GlyGlyCys(15) (KD = 10(-17.4) M at pH 7.0) and delivers copper to the trans-Golgi network (TGN). Atox1 may participate in the metabolism of the drug cis-Pt(NH3)2Cl2 (cisplatin), either as a component of its delivery to the nucleus or of its loss via transport to the TGN and beyond. The species of stoich...

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Probing the interaction of cisplatin with the human copper chaperone Atox1 by solution and in-cell NMR spectroscopy.

Among anticancer therapeutics, platinum-based drugs have a prominent role. They carry out their antitumor activity by forming stable adducts with DNA, thus interfering with replication and transcription processes. Cellular uptake of these drugs is tightly connected to copper transport. The major Cu(I) influx transporter Ctr1 has been found to mediate transport of cisplatin and its analogues. Ev...

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Conserved residues modulate copper release in human copper chaperone Atox1.

It is unclear how the human copper (Cu) chaperone Atox1 delivers Cu to metal-binding domains of Wilson and Menkes disease proteins in the cytoplasm. To begin to address this problem, we have characterized Cu(I) release from wild-type Atox1 and two point mutants (Met(10)Ala and Lys(60)Ala). The dynamics of Cu(I) displacement from holo-Atox1 were measured by using the Cu(I) chelator bicinchonic a...

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ژورنال

عنوان ژورنال: Protein & Peptide Letters

سال: 2013

ISSN: 0929-8665

DOI: 10.2174/09298665113209990036