TY - JOUR
T1 - Effects of Cu(II) and cisplatin on the stability of Specific protein 1 (Sp1)-DNA binding
T2 - Insights into the regulation of copper homeostasis and platinum drug transport
AU - Yan, Dong
AU - Aiba, Isamu
AU - Chen, Helen H.W.
AU - Kuo, Macus Tien
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jinorgbio.2016.04.030
DO - 10.1016/j.jinorgbio.2016.04.030
M3 - Article
C2 - 27172866
AN - SCOPUS:84974696007
SN - 0162-0134
VL - 161
SP - 37
EP - 39
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -