DNA damage induced p53 downregulates Cdc20 by direct binding to its promoter causing chromatin remodeling.
DNA damage induced p53 downregulates Cdc20 by direct binding to its promoter causing chromatin remodeling.
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DNA损伤通过直接结合其启动子引起染色质重塑，从而诱导p53降低CDC20。
DOI：
10.1093/nar/gkp110
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发表时间：
2009-05
影响因子：
14.9
通讯作者：
Roychoudhury S
中科院分区：
文献类型：
--
作者：
Banerjee T;Nath S;Roychoudhury S
CDC 20是主轴组装检查点（SAC）中的关键分子。它激活后期促进复合物，并帮助分裂细胞进行后期。CDC 20在许多肿瘤细胞中过表达，导致染色体不稳定。关于SAC对遗传毒性应激反应的机制报道有限。我们发现，异位表达的p53或DNA损伤诱导内源性p53可以下调Cdc 20的转录。我们已经确定了一个共识p53的Cdc 20启动子上的结合位点，并已表明，它是由p53结合的启动子，并带来染色质重塑，从而抑制Cdc 20。此外，p53也通过CDE/CD 4元件下调Cdc 20启动子，但不依赖于p21。这种CDE/p53元件介导的下调仅发生在p53过表达的条件下，而不是在DNA损伤的情况下。目前的结果表明，Cdc 20启动子中的两个CCAAT元件不被p53用来下调其活性，如前所述。
CDC20 is a critical molecule in the Spindle Assembly Checkpoint (SAC). It activates the Anaphase promoting complex and helps a dividing cell to proceed towards Anaphase. CDC20 is overexpressed in many tumor cells which cause chromosomal instability. There have been limited reports on the mechanism of SAC's response to genotoxic stress. We show that ectopically expressed p53 or DNA damage induced endogenous p53 can downregulate Cdc20 transcriptionally. We have identified a consensus p53-binding site on the Cdc20 promoter and have shown that it is being used by p53 to bind the promoter and bring about chromatin remodeling thereby repressing Cdc20. Additionally, p53 also downregulates Cdc20 promoter through CDE/CHR element, but in a p21 independent manner. This CDE/CHR element-mediated downregulation occurs only under p53 overexpressed condition but not in the context of DNA damage. The present results suggest that the two CCAAT elements in the Cdc20 promoter are not used by p53 to downregulate its activity, as reported earlier.
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