Involvement of protein kinase in environmental stress‐induced activation of human multidrug resistance 1 (MDR1) gene promoter
Involvement of protein kinase in environmental stress‐induced activation of human multidrug resistance 1 (MDR1) gene promoter
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蛋白激酶参与环境应激诱导的人类多药耐药 1 (MDR1) 基因启动子激活
DOI：
10.1016/0014-5793(93)81750-t
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发表时间：
1993
期刊：
影响因子：
3.5
通讯作者：
M. Kuwano
中科院分区：
文献类型：
--
作者：
T. Uchiumi;K. Kohno;H. Tanimura;K. Hidaka;K. Asakuno;H. Abe;Yuzo Uchida;M. Kuwano
人MDR 1基因可以响应于各种环境刺激而被诱导。为了检查这种应激诱导的MDR 1基因激活是否可以通过蛋白激酶调节，我们采用了一种稳定的人癌KB细胞系，该细胞系含有由MDR 1基因启动子指导的细菌氯霉素乙酰转移酶（CAT）基因。H-7是一种蛋白激酶C抑制剂，浓度超过40 μM时，可抑制甲基磺酸乙酯、5-氟尿嘧啶或紫外线照射诱导的MDR 1启动子活化。在用UV处理的KB细胞中，识别MDR 1启动子的核因子的DNA结合活性增强，但在同时用H-7处理的细胞中降低。冈田酸单独能够诱导启动子激活，并且这种诱导依赖于特定的启动子序列。冈田酸还增强了识别MDR 1启动子的核因子的DNA结合活性。反式作用因子的磷酸化可调节MDR 1基因启动子的活性。
The human MDR1 gene can be induced in response to various environmental stimuli. To examine whether such stress‐induced activation of the MDR1 gene can be modulated by protein kinase, we employed a stable human cancer KB cell line which contained the bacterial chloramphenicol acetyltransferase (CAT) gene directed by the MDR1 gene promoter. H‐7, a protein kinase C inhibitor, at more than 40 μM inhibited activation of the MDR1 promoter that was induced by ethylmethane sulfonate, 5‐fluorouracil or UV irradiation. DNA binding activity of nuclear factors recognizing the MDR1 promoter was augmented in KB cells treated with UV, but decreased in cells treated concomitantly with H‐7. Okadaic acid alone was able to induce the promoter activation, and this induction was dependent on specific promoter sequences. Okadaic acid also enhanced the DNA binding activity of nuclear factors recognizing the MDR1 promoter. The phosphorylation of transacting factors may modulate the MDR1 gene promoter activity.