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首页> 外文期刊>Oncogene >Role of DREF in transcriptional regulation of the Drosophila p53 gene
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Role of DREF in transcriptional regulation of the Drosophila p53 gene

机译:DREF在果蝇p53基因转录调控中的作用

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摘要

The tumor suppressor protein p53 has a critical role in safeguarding the integrity of the genome. Its functions are well understood but factors responsible for the transcriptional regulation of the p53 gene are almost entirely unknown. The DNA replication-related element (DRE)/DNA replication-related element-binding factor (DREF) transcriptional regulatory system is established as a master key to cell proliferation in Drosophila. DREF binds specifically to DRE sequences in the Drosophila p53 (dmp53) gene promoter as shown using anti-DREF antibodies in chromatin immunoprecipitation assays. Furthermore, a rough eye phenotype because of overexpression of DREF in Drosophila eye imaginal disks could be suppressed by half dose reduction of the dmp53 gene. In addition, the level of mRNA of dmp53 was decreased in DREF-knockdown cells and transient expression of the luciferase gene under control of the wild-type dmp53 gene promoter showed strong promoter activity in S2 cells, but this was almost completely abrogated with a DRE-mutated promoter. Requirement of DREs for dmp53 promoter activity was further confirmed by anti-β-galactosidase antibody-staining of various tissues from transgenic flies carrying dmp53 promoter-lacZ fusion genes. These results indicate that DREF is necessary for dmp53 gene promoter activity.
机译:肿瘤抑制蛋白p53在维护基因组完整性方面具有至关重要的作用。它的功能已广为人知,但几乎完全未知负责p53基因转录调控的因素。 DNA复制相关元件(DRE)/ DNA复制相关元件结合因子(DREF)转录调节系统被确立为果蝇细胞增殖的主键。 DREF与果蝇p53(dmp53)基因启动子中的DRE序列特异性结合,如在染色质免疫沉淀试验中使用抗DREF抗体所示。此外,由于果蝇眼成像盘中DREF的过表达而导致的粗糙眼表型可以通过减少dmp53基因剂量的一半来抑制。此外,在DREF-knockdown细胞中,dmp53的mRNA水平降低,在野生型dmp53基因启动子控制下的荧光素酶基因瞬时表达在S2细胞中显示出强大的启动子活性,但DRE几乎完全消除了该活性突变的启动子。 DRE对dmp53启动子活性的要求已通过对带有dmp53启动子-lacZ融合基因的转基因果蝇的各种组织进行抗β-半乳糖苷酶抗体染色进一步证实。这些结果表明DREF是dmp53基因启动子活性所必需的。

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