The thioredoxin/thioredoxin reductase redox system and control of cell growth.
The thioredoxin/thioredoxin reductase redox system and control of cell growth.
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发表时间：
1994
影响因子：
3.1
通讯作者：
Garth Powis;J. Oblong;P. Gasdaska;M. Berggren;Simon R. Hill;D. Kirkpatrick
中科院分区：
文献类型：
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作者：
Garth Powis;J. Oblong;P. Gasdaska;M. Berggren;Simon R. Hill;D. Kirkpatrick
硫氧还蛋白是一种氧化还原蛋白，对多种细胞内功能非常重要，可能包括对转录因子活性的调节。我们已经证明，人类硫氧还蛋白与成人T细胞来源的白血病细胞生长因子具有相同的预测氨基酸序列。重组人硫氧还蛋白刺激瑞士小鼠3T3成纤维细胞增殖，其EC50为100 nM，并可刺激多个人类癌细胞的增殖。硫氧还蛋白活性部位半胱氨酸的定点突变研究表明，氧化还原活性是刺激细胞增殖所必需的。添加的125I-硫氧还蛋白在培养中被细胞摄取，并可能具有细胞内作用。一系列烷基2-咪唑基二硫化物被证明是人硫氧还蛋白还原酶的竞争性抑制剂，其KI值为3.3~8.6微米。其中一种化合物抑制瑞士3T3硫氧还蛋白依赖的增殖，IC50值为60 nM。
Thioredoxin is a redox protein that is important for a variety of intracellular functions, possibly including regulation of transcription factor activity. We have shown that human thioredoxin has the same predicted amino acid sequence as adult T-cell-derived leukemic cell growth factor. Recombinant human thioredoxin stimulates the proliferation of Swiss murine 3T3 fibroblasts with an EC50 of 100 nM and the proliferation of a number of human cancer cells. Site-directed mutagenesis of the active-site cysteines of thioredoxin has shown that redox activity is necessary for the stimulation of cell proliferation. Added 125I-thioredoxin is taken up by cells in culture and could have intracellular action. A series of alkyl 2-imidazolyl disulfides have been shown to be competitive inhibitors of human thioredoxin reductase with Ki values of 3.3 to 8.6 microM. The compounds inhibited Swiss 3T3 serum-dependent proliferation with IC50 values of 2.0 to 4.0 microM, and one compound inhibited Swiss 3T3 thioredoxin-dependent proliferation with an IC50 value of 60 nM.