...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >Phosphorylated Sp1 is the regulator of DNA-PKcs and DNA ligase IV transcription of daunorubicin-resistant leukemia cell lines
【24h】

Phosphorylated Sp1 is the regulator of DNA-PKcs and DNA ligase IV transcription of daunorubicin-resistant leukemia cell lines

机译：磷酸化的Sp1是耐柔红霉素的白血病细胞系DNA-PKcs和DNA连接酶IV转录的调节剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Multidrug resistance (MDR) is a serious problem faced in the treatment of malignant tumors. In this study, we characterized the expression of non-homologous DNA end joining (NHEJ) components, a major DNA double strand break (DSB) repair mechanism in mammals, in K562 cell and its daunorubicin (DNR)-resistant subclone (K562/DNR). K562/DNR overexpressed major enzymes of NHEJ, DNA-PKcs and DNA ligase IV, and K562/DNR repaired DSB more rapidly than K562 after DNA damage by neocarzinostatin (MDR1-independent radiation-mimetic). Overexpressed DNA-PKcs and DNA ligase IV were also observed in DNR-resistant HL60 (HL60/DNR) cells as compared with parental HL60 cells. Expression level of DNA-PKcs mRNA paralleled its protein level, and the promoter activity of DNA-PKcs of K562/DNR was higher than that of K562, and the 5'-region between - 49. bp and the first exon was important for its activity. Because this region is GC-rich, we tried to suppress Sp1 family transcription factor using mithramycin A (MMA), a specific Sp1 family inhibitor, and siRNAs for Sp1 and Sp3. Both MMA and siRNAs suppressed DNA-PKcs expression. Higher serine-phosphorylated Sp1 but not total Sp1 of both K562/DNR and HL60/DNR was observed compared with their parental K562 and HL60 cells. DNA ligase IV expression of K562/DNR was also suppressed significantly with Sp1 family protein inhibition. EMSA and ChIP assay confirmed higher binding of Sp1 and Sp3 with DNA-PKcs 5'-promoter region of DNA-PKcs of K562/DNR than that of K562. Thus, the Sp1 family transcription factor affects important NHEJ component expressions in anti-cancer drug-resistant malignant cells, leading to the more aggressive MDR phenotype.
机译：多药耐药性（MDR）是恶性肿瘤治疗中面临的严重问题。在这项研究中，我们表征了K562细胞及其耐柔红霉素（DNR）的亚克隆（K562 / DNR）中非同源DNA末端连接（NHEJ）成分的表达，这是哺乳动物中主要的DNA双链断裂（DSB）修复机制。 ）。 K562 / DNR过度表达NHEJ，DNA-PKcs和DNA连接酶IV的主要酶，并且在新卡他汀抑制DNA损伤后，K562 / DNR修复DSB的速度比K562快（不依赖MDR1的辐射模拟物）。与亲本HL60细胞相比，在耐DNR的HL60（HL60 / DNR）细胞中也观察到过表达的DNA-PKcs和DNA连接酶IV。 DNA-PKcs mRNA的表达水平与其蛋白水平平行，并且K562 / DNR的DNA-PKcs启动子活性高于K562，且-49. bp与第一个外显子之间的5'区域对其重要。活动。由于该区域富含GC，因此我们尝试使用特异的Sp1家族抑制剂丝裂霉素A（MMA）和Sp1和Sp3的siRNA来抑制Sp1家族转录因子。 MMA和siRNA均抑制DNA-PKcs表达。与亲本的K562和HL60细胞相比，观察到K562 / DNR和HL60 / DNR的丝氨酸磷酸化Sp1更高，但总Sp1更高。 Sp1家族蛋白抑制也显着抑制了K562 / DNR的DNA连接酶IV表达。 EMSA和ChIP试验证实，Sp1和Sp3与K562 / DNR的DNA-PKcs的DNA-PKcs 5'启动子区域的结合高于K562。因此，Sp1家族转录因子影响抗癌药物耐药性恶性细胞中重要的NHEJ成分表达，从而导致更具攻击性的MDR表型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号