The role of Ctr1 and Ctr2 in mammalian copper homeostasis and platinum-based chemotherapy.
The role of Ctr1 and Ctr2 in mammalian copper homeostasis and platinum-based chemotherapy.
复制标题
DOI：
10.1016/j.jtemb.2014.03.006
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Thiele DJ
中科院分区：
文献类型：
--
作者：
Öhrvik H;Thiele DJ
铜（Cu）是生长和发育所必需的金属，如果铜的积累水平超过细胞体内平衡吸收与解毒的能力，则铜可能有毒。一个系统的铜收购是完整的膜铜+转运蛋白，Ctr1，这已经相当好的特点，在其功能和生理。哺乳动物Ctr2蛋白一直是铜领域的难题，因为它在结构上与高亲和力铜转运蛋白Ctr1密切相关，共享铜转运活性的重要基序。然而，与哺乳动物Ctr1相反，Ctr2未能抑制Cu+输入缺陷的酵母细胞的Cu依赖性生长表型，也没有明显刺激Cu收购时，在哺乳动物细胞中过表达，强调了两种蛋白质之间的重要功能差异。哺乳动物Ctr2的几种作用已经在体外和体内被提出。在这里，我们总结和讨论目前的见解Ctr2蛋白及其相互作用与Ctr1，其功能在哺乳动物铜稳态和铂为基础的化疗。
Copper (Cu) is an essential metal for growth and development that has the potential to be toxic if levels accumulate beyond the ability of cells to homeostatically balance uptake with detoxification. One system for Cu acquisition is the integral membrane Cu+ transporter, Ctr1, which has been quite well characterized in terms of its function and physiology. The mammalian Ctr2 protein has been a conundrum for the copper field, as it is structurally closely related to the high affinity Cu transporter Ctr1, sharing important motifs for Cu transport activity. However, in contrast to mammalian Ctr1, Ctr2 fails to suppress the Cu-dependent growth phenotype of yeast cells defective in Cu+ import, nor does it appreciably stimulate Cu acquisition when over-expressed in mammalian cells, underscoring important functional dissimilarities between the two proteins. Several roles for the mammalian Ctr2 have been suggested both in vitro and in vivo. Here, we summarize and discuss current insights into the Ctr2 protein and its interaction with Ctr1, its functions in mammalian Cu homeostasis and platinum-based chemotherapy.