Low-affinity copper transporter CTR2 is regulated by copper-sensing transcription factor Mac1p in Saccharomyces cerevisiae
Low-affinity copper transporter CTR2 is regulated by copper-sensing transcription factor Mac1p in Saccharomyces cerevisiae
复制标题
酿酒酵母中低亲和力铜转运蛋白 CTR2 受铜感应转录因子 Mac1p 调节
DOI：
10.1016/j.bbrc.2012.03.040
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发表时间：
2012-04-13
影响因子：
3.1
通讯作者：
Li, Chenghua
中科院分区：
文献类型：
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作者：
Liu, Lihua;Qi, Jin;Li, Chenghua
铜是生命中不可缺少的金属。由于酵母菌具有与哺乳动物细胞相似的金属代谢途径，便于基因操作，因此被广泛用于金属稳态的研究。铜离子在酵母液泡或哺乳动物溶酶体中的储存和移动对于细胞避免其毒性和提高其利用率是重要的。虽然铜稳态中涉及的其他基因的调节是很好理解的，但编码低亲和力铜转运蛋白Ctr2p的基因的调节仍然不清楚，该基因介导液泡或溶酶体储存的铜离子的动员。在本研究中，我们发现铜缺乏可上调酵母细胞CTR 2基因的转录，而铜过量可下调该基因的转录，并且铜敏感转录因子Mac1p的基因缺失可消除铜缺乏诱导的CTR 2基因的转录。虽然缺乏共识Mad p结合序列，CTR 2启动子区被Mac1p占据，根据我们的染色质免疫沉淀（ChIP）试验的结果。Mac1p的过表达可以上调CTR 2的转录，并部分弥补铜缺陷酵母菌株的生长缺陷。两者合计，我们的研究结果表明，Mac1p可以激活空泡铜转运蛋白Ctr2p的表达，响应铜缺乏，导致酵母耐铜饥饿。(C)2012 Elsevier Inc. All rights reserved.
Copper is an indispensable metal for life. For convenience of genetic manipulation and sharing similar metabolic pathway of metals with mammalian cells, the yeast Saccharomyces cerevisiae is widely used for metal homeostasis studies. Storage and mobilization of copper ions in yeast vacuoles or mammalian lysosomes are important for cells to avoid their toxicity and elevate their utility. Though regulation of other genes involved in copper homeostasis is well understood, the regulation of gene encoding low-affinity copper transporter Ctr2p, which mediates mobilization of vacuolar or lysosomal stored copper ions, is still unclear. In this study, we found that copper depletion can upregulate yeast CTR2 gene transcription while copper overload downregulate it. The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p. Though absent of consensus Mad p binding sequences, CTR2 promoter region is demonstrated to be occupied by Mac1p, according to our results of chromatin immunoprecipitation (ChIP) assay. Overexpression of Mac1p can upregulate CTR2 transcription and partially complement the growth defect of copper-deficient yeast strain. Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation. (C) 2012 Elsevier Inc. All rights reserved.