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Conference Paper: Comparison between copper and cisplatin transport mediated by human copper transporter 1 (hCTR1)
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TitleComparison between copper and cisplatin transport mediated by human copper transporter 1 (hCTR1)
 
AuthorsDu, X2 1
Wang, X2
Li, H2
Sun, H2
 
Issue Date2012
 
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/Publishing/Journals/MT/About.asp
 
CitationMetallomics, 2012, v. 4 n. 7, p. 679-685 [How to Cite?]
DOI: http://dx.doi.org/10.1039/c2mt20021j
 
AbstractCopper transporter 1 (CTR1) is a transmembrane protein that imports copper(i) into yeast and mammalian cells. Surprisingly, the protein also mediates the uptake of platinum anticancer drugs, e.g. cisplatin and carboplatin. To study the effects of several metal-binding residues/motifs of hCTR1 on the transport of both Cu + and cisplatin, we have constructed Hela cells that stably express a series of hCTR1 variant proteins including H22-24A, NHA, C189S, hCTR1ΔC, H139R and Y156A, and compared their abilities to regulate the accumulation and cytotoxicity of these metal compounds. Our results demonstrated that the cells expressing the hCTR1 mutants of histidine-rich motifs in the N-terminus (H22-24A, NHA) resulted in a higher basal copper level in the steady state compared to those expressing wild-type protein. However, the cellular accumulation of both copper and cisplatin in these variants was found at a similar level to that of wild type when incubated with an excess of metal compounds (100 μM). The cells expressing hCTR1 variants of H139R and Y156A exhibit lower capacities towards accumulation of copper but not cisplatin. Significantly, cells with the C189S variant partially retained the ability of the wild-type hCTR1 protein to accumulate both copper and cisplatin, while for cells expressing the C-terminus truncated variant of hCTR1 (hCTR1ΔC) this ability was absolutely abolished, suggesting that this motif is crucial for the function of the transporter. This journal is © 2012 The Royal Society of Chemistry.
 
ISSN1756-5901
2012 Impact Factor: 4.099
 
DOIhttp://dx.doi.org/10.1039/c2mt20021j
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorDu, X
 
dc.contributor.authorWang, X
 
dc.contributor.authorLi, H
 
dc.contributor.authorSun, H
 
dc.date.accessioned2012-08-16T05:48:57Z
 
dc.date.available2012-08-16T05:48:57Z
 
dc.date.issued2012
 
dc.description.abstractCopper transporter 1 (CTR1) is a transmembrane protein that imports copper(i) into yeast and mammalian cells. Surprisingly, the protein also mediates the uptake of platinum anticancer drugs, e.g. cisplatin and carboplatin. To study the effects of several metal-binding residues/motifs of hCTR1 on the transport of both Cu + and cisplatin, we have constructed Hela cells that stably express a series of hCTR1 variant proteins including H22-24A, NHA, C189S, hCTR1ΔC, H139R and Y156A, and compared their abilities to regulate the accumulation and cytotoxicity of these metal compounds. Our results demonstrated that the cells expressing the hCTR1 mutants of histidine-rich motifs in the N-terminus (H22-24A, NHA) resulted in a higher basal copper level in the steady state compared to those expressing wild-type protein. However, the cellular accumulation of both copper and cisplatin in these variants was found at a similar level to that of wild type when incubated with an excess of metal compounds (100 μM). The cells expressing hCTR1 variants of H139R and Y156A exhibit lower capacities towards accumulation of copper but not cisplatin. Significantly, cells with the C189S variant partially retained the ability of the wild-type hCTR1 protein to accumulate both copper and cisplatin, while for cells expressing the C-terminus truncated variant of hCTR1 (hCTR1ΔC) this ability was absolutely abolished, suggesting that this motif is crucial for the function of the transporter. This journal is © 2012 The Royal Society of Chemistry.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationMetallomics, 2012, v. 4 n. 7, p. 679-685 [How to Cite?]
DOI: http://dx.doi.org/10.1039/c2mt20021j
 
dc.identifier.doihttp://dx.doi.org/10.1039/c2mt20021j
 
dc.identifier.epage685
 
dc.identifier.hkuros205082
 
dc.identifier.issn1756-5901
2012 Impact Factor: 4.099
 
dc.identifier.issue7
 
dc.identifier.openurl
 
dc.identifier.pmid22552365
 
dc.identifier.scopuseid_2-s2.0-84863683148
 
dc.identifier.spage679
 
dc.identifier.urihttp://hdl.handle.net/10722/159379
 
dc.identifier.volume4
 
dc.languageeng
 
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/Publishing/Journals/MT/About.asp
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofMetallomics
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.titleComparison between copper and cisplatin transport mediated by human copper transporter 1 (hCTR1)
 
dc.typeConference_Paper
 
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Author Affiliations
  1. Shenzhen University
  2. The University of Hong Kong