Tumor suppressor p53 is required to modulate BRCA1 expression
Tumor suppressor p53 is required to modulate BRCA1 expression
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DOI：
10.1128/mcb.20.20.7450-7459.2000
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发表时间：
2000-10-01
影响因子：
5.3
通讯作者：
Lee, SW
中科院分区：
文献类型：
--
作者：
Arizti, P;Fang, L;Lee, SW
携带BRCA 1或p53基因突变的个体易患多种癌症，这两种肿瘤抑制基因都与DNA损伤反应途径有关。我们分析了p53和BRCA 1基因之间可能的功能联系。在这里，我们表明，BRCA 1的表达水平下调响应p53诱导细胞经历生长停滞，衰老，或凋亡。生理刺激，如暴露于DNA损伤剂，也导致BRCA 1水平的负调节在p53依赖性的方式之前，引起细胞周期停滞。核运行实验和荧光素酶报告基因分析表明，BRCA 1表达的变化主要是由于p53诱导的转录抑制。总之，这些数据表明，BRCA 1的表达水平是由野生型p53的存在和活性控制，并表明细胞内的p53/BRCA 1通路的存在，在细胞的应激条件的反应。
Individuals carrying mutations in BRCA1 or p53 genes are predisposed to a variety of cancers, and both tumor suppressor genes have been implicated in DNA damage response pathways. We have analyzed a possible functional link between p53 and BRCA1 genes. Here we show that BRCA1 expression levels are down-regulated in response to p53 induction in cells that undergo either growth arrest, senescence, or apoptosis. Physiological stimuli, such as exposure to DNA-damaging agents, also result in negative regulation of BRCA1 levels in a p53-dependent manner prior to causing cell cycle arrest. Nuclear run-on experiments and luciferase reporter assays demonstrate that the changes in BRCA1 expression are mainly due to transcriptional repression induced by p53. In conclusion, the data show that BRCA1 expression levels are controlled by the presence and activity of wild-type p53 and suggest the existence of an intracellular p53/BRCA1 pathway in the response of cells to stress conditions.