Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90
Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90
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DOI：
10.1016/j.febslet.2008.10.029
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发表时间：
2008-11-26
期刊：
影响因子：
3.5
通讯作者：
Itoh, Hideaki
中科院分区：
文献类型：
--
作者：
Ishida, Ryuichi;Takaoka, Yuka;Itoh, Hideaki
90-kDa热休克蛋白(HSP90)是一种分子伴侣，在胞浆中协助蛋白质的折叠和组装。我们先前证明了抗肿瘤试剂顺铂抑制哺乳动物HSP90的聚集抑制活性。我们现在发现顺铂结合了人HSP90的氨基末端和羧基末端区域，并且对这两个区域有不同的影响。顺铂阻断HSP90C的聚集抑制作用，但不能阻断HSP90N的聚集抑制作用。相反，顺铂可诱导HSP90N的构象改变，但不能改变HSP90C的构象。这些结果表明，顺铂通过HSP90分子的两个不同的结合部位通过两种不同的机制调节HSP90的活性。(C)2008年欧洲生化学会联合会。爱思唯尔出版，版权所有。
The 90-kDa heat shock protein (HSP90) is a molecular chaperone that assists in the folding and assembly of proteins in the cytosol. We previously demonstrated that the antineoplastic reagent, cisplatin, inhibits the aggregation prevention activity of mammalian HSP90. We now show that cisplatin binds both the amino terminal and carboxyl terminal domains of the human HSP90 and differently affects these two domains. Cisplatin blocks the aggregation prevention activity of HSP90C, but not HSP90N. In contrast, cisplatin induces a conformational change in HSP90N, but not HSP90C. These results indicate that cisplatin modulates the HSP90 activities through two different mechanisms using the two distinct binding sites of the HSP90 molecule. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.