BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance
BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance
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DOI：
10.1016/s1097-2765(01)00357-4
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发表时间：
2001-10-01
期刊：
影响因子：
16
通讯作者：
Skorski, T
中科院分区：
文献类型：
--
作者：
Slupianek, A;Schmutte, C;Skorski, T
RAD 51是大肠杆菌的六个有丝分裂人类同源物之一。大肠杆菌RecA蛋白（RAD 51-Paralogs）在同源重组和DNA双链断裂（DSB）修复中起核心作用。在这里，我们表明，RAD 51是重要的耐顺铂和丝裂霉素C的细胞表达BCR/ABL致癌酪氨酸激酶。BCR/ABL显著增强了RAD 51和几种RAD 51-Paralogs的表达。RAD 51过表达由STAT 5依赖性转录以及抑制半胱天冬酶-3依赖性切割介导。BCR/ABL对RAD 51 Tyr-315残基的磷酸化对于增强DSB修复和耐药性似乎是必不可少的。哺乳动物RecA同源物的诱导在由致癌酪氨酸激酶转化的哺乳动物细胞中建立了DNA损伤抗性的独特机制。
RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD51-Paralogs) that play a central role in homologous recombination and repair of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is important for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expression of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-dependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase.