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首页> 外文期刊>Cellular Signalling >xCT expression reduces the early cell cycle requirement for calcium signaling
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xCT expression reduces the early cell cycle requirement for calcium signaling

机译:XCT表达减少了钙信号传导的早期细胞周期要求

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Calcium has long been recognized as an important regulator of cell cycle transitions although the mechanisms are largely unknown. A functional genomic screen has identified genes involved in the regulation of early cell cycle progression by calcium. These genes when overexpressed confer the ability to bypass the G1/S arrest induced by Ca2+-channel antagonists in mouse fibroblasts. Overexpression of the cystine-glutamate exchanger, xCT, bad the greatest ability to evade calcium antagonist-induced cell cycle arrest. xCT carries out the rate limiting step of glutathione synthesis in many cell types and is responsible for the uptake of cystine in most human cancer cell lines. Functional analysis indicates that the cystine uptake activity of xCT overcomes the G1/S arrest induced by Ca2+-channel antagonists by bypassing the requirement for calcium signaling. Since cells overexpressing xCT were found to have increased levels and activity of the AP-1 transcription factor in G1, redox stimulation of AP-1 activity accounts for the observed growth of these cells in the presence of calcium channel antagonists. These results suggest that reduced calcium signaling impairs AP-1 activation and that xCT expression may directly affect cell proliferation. (C) 2007 Elsevier Inc. All rights reserved.
机译:钙已经被认为是细胞周期过渡的重要调节因子,尽管机制很大程度上是未知的。功能基因组筛网已经通过钙来确定参与早期细胞周期进展的基因。过表达赋予在小鼠成纤维细胞中绕过Ca2 + -Channel拮抗剂诱导的G1 / S停滞的能力的这些基因。过表达胱氨酸 - 谷氨酸交换剂,XCT,避免钙拮抗剂诱导的细胞周期停滞的最大能力。 XCT通过许多细胞类型进行谷胱甘肽合成的速率限制步骤,并负责在大多数人类癌细胞系中的胱氨酸摄取。功能分析表明XCT的胱氨酸摄取活性克服了Ca2 + -Channel拮抗剂诱导的G1 / S停滞通过绕过钙信号传导的要求。由于发现过表达XCT的细胞具有增加的G1中AP-1转录因子的水平和活性,因此AP-1活性的氧化还原刺激估计在钙通道拮抗剂存在下观察到这些细胞的生长。这些结果表明,降低的钙信号传导损害AP-1激活,并且XCT表达可以直接影响细胞增殖。 (c)2007年elestvier Inc.保留所有权利。

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