INDUCTION OF P53-LIKE, MDM2-LIKE, AND WAF1/CIP1-LIKE MOLECULES IN INSECT CELLS BY DNA-DAMAGING AGENTS
INDUCTION OF P53-LIKE, MDM2-LIKE, AND WAF1/CIP1-LIKE MOLECULES IN INSECT CELLS BY DNA-DAMAGING AGENTS
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DOI：
10.1006/excr.1995.1120
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发表时间：
1995-04-01
影响因子：
3.7
通讯作者：
FORNACE, AJ
中科院分区：
文献类型：
--
作者：
BAE, I;SMITH, ML;FORNACE, AJ
DNA 损伤后的细胞反应在生物界中无处不在。为了应对 DNA 损伤，细胞周期检查点被激活，从而延迟细胞周期进程，并很可能为修复留出时间。哺乳动物细胞中的一个重要检查点在细胞周期的 G(1) 期激活，依赖于 p53 肿瘤抑制基因产物。虽然 p53 负责诱导 G(1) 停滞，但 MDM2 基因的产物被认为可以减轻停滞，从而允许细胞周期在短暂延迟后继续进行。由于 MDM2 和 WAF1/CTP1 被 p53 反式激活，而 MDM2 结合并调节 p53 的活性，因此创建了“反馈环”。该途径在哺乳动物细胞中高度保守，但其在脊椎动物之外的存在尚不清楚。通过使用人类 MDM2 和 WAF1/CIP1 cDNA 探针以及 p53 和 Mdm2 的单克隆抗体，我们在昆虫细胞系中证明了 p53-、MDM2- 和 WAF1/CIP1 样分子以及 DNA 损伤剂处理后 p53 调节途径的存在。 (C) 1995 学术出版社
Cellular responses following DNA damage are ubiquitous in the biological world. In response to DNA damage, cell cycle checkpoints are activated, which delay cell cycle progression and most likely serve to allow time for repair. One important checkpoint in mammalian cells, activated in the G(1) phase of the cell cycle, is dependent on the p53 tumor suppressor gene product. While p53 is responsible for inducing G(1) arrest, the product of the MDM2 gene is believed to alleviate the arrest, allowing continuation of the cell cycle after a transient delay. Inasmuch as MDM2 and WAF1/CTP1 are transactivated by p53, while MDM2 binds to and modulates the activity of p53, a ''feedback loop'' is thus created. This pathway has been highly conserved in mammalian cells, but its presence outside of vertebrates is unknown. By using human MDM2 and WAF1/CIP1 cDNA probes, and monoclonal antibodies to p53 and Mdm2, we demonstrate in insect cell lines evidence for the existence of p53-, MDM2-, and WAF1/CIP1-like molecules and a p53-regulated pathway following treatment by DNA-damaging agents. (C) 1995 Academic Press, Inc.