title: Effects of Cu(II) and cisplatin on the stability of Specific protein 1 (Sp1)-DNA binding: Insights into the regulation of copper homeostasis and platinum drug transport.
abstract: The human high-affinity copper transporter 1 (hCtr1) transports both Cu(I) and cisplatin (cDDP). Because Cu deficiency is lethal yet Cu overload is poisonous, hCtr1 expression is transcriptionally upregulated in response to Cu deficiency but is downregulated under Cu replete conditions in controlling Cu homeostasis. The up- and down-regulation of hCtr1 is regulated by Specific protein 1 (Sp1), which itself is also correspondingly regulated under these Cu conditions. hCtr1 expression is also upregulated by cDDP via upregulation of Sp1. The underlying mechanisms of these regulations are unknown. Using gel-electrophoretic mobility shift assays, we demonstrated here that Sp1-DNA binding affinity is reduced under Cu replete conditions but increased under reduced Cu conditions. Similarly, Sp1-DNA binding affinity is increased by cDDP treatment. This in vitro system demonstrated, for the first time, that regulation of Sp1/hCtr1 expression by these agents is modulated by the stability of Sp1-DNA binding, the first step in the Sp1-mediated transcriptional regulation process.
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States; Department of Oncology, Beijing Chao-Yang Hospital affiliated with Capital Medical University, No.8 Gongti South Street, Beijing 100020, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Isamu
authors.initials: I
authors.lastname: Aiba
authors.affiliation: Department of Radiation Oncology, National Cheng Kung University, National Cheng Kung University Hospital, College of Medicine, Tainan 70428, Taiwan.
authors.forename: Helen H W
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Electronic address: tkuo@mdanderson.org.
authors.forename: Macus Tien
authors.initials: MT
authors.lastname: Kuo
mesh_terms: D001693:Biological Transport, Active; D027682:Cation Transport Proteins / Q000096:biosynthesis; D002945:Cisplatin / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D000079923:Copper Transporter 1; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D016329:Sp1 Transcription Factor / Q000737:chemistry* / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C490079:SLC31A1 protein, human; D016329:Sp1 Transcription Factor; D003300:Copper; D004247:DNA; D002945:Cisplatin
keywords: Cisplatin; Copper homeostasis; Cu(II); High-affinity copper transporter (hCtr1); Specific protein (Sp1)