p53 regulates cellular resistance to complement lysis through enhanced expression of CD59(Retracted article. See vol. 73, pg. 6838, 2013)
p53 regulates cellular resistance to complement lysis through enhanced expression of CD59(Retracted article. See vol. 73, pg. 6838, 2013)
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DOI：
10.1158/0008-5472.can-05-3191
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发表时间：
2006-02-15
期刊：
影响因子：
11.2
通讯作者：
Morgan, BP
中科院分区：
文献类型：
--
作者：
Donev, RM;Cole, DS;Morgan, BP
最近有假设认为CD59基因有两个p53应答元件，可能参与防御宿主细胞免受炎症中补体系统的损伤。在这里，我们研究了CD59基因中这些假定的p53结合序列在调节CD59表达中的作用。我们已经证明这两种潜在的反应元件在体外结合p53。使用小干扰RNA敲除p53的表达导致HeLa细胞中CD59蛋白表达降低6倍。我们之前观察到喜树碱诱导的凋亡IMR32细胞中CD59的表达减少，而与未处理的细胞相比，存活部分的表达增加。在这里，我们已经证明这些变化与p53的表达水平和乙酰化状态的改变有关。我们还表明，在暴露于炎症细胞因子的细胞上，p53的乙酰化状态调节CD59的表达，从而模拟炎症。我们的数据表明，p53和体内p53的阳性/阴性调节因子可用于调节肿瘤细胞对化疗补体溶解的敏感性。
It has been recently hypothesized that the CD59 gene has two putative p53-responsive elements that may be involved in defense of host cells from damage by the complement system in inflammation. Here we have examined the roles of these putative p53-binding sequences within the CD59 gene in regulation of CD59 expression. We have shown that both of these potential responsive elements bind p53 in vitro. Knocking down expression of p53 using small interfering RNA led to a 6-fold decrease in CD59 protein expression in HeLa cells. We have previously observed a decrease of CD59 in camptothecin-induced apoptotic IMR32 cells, whereas expression was increased in the surviving fraction compared with untreated cells. Here, we have shown that these changes are associated with altered expression levels and acetylation status of p53. We have also shown that acetylation status of p53 regulates CD59 expression on cells exposed to inflammatory cytokines to model inflammation. Our data suggest that p53 and in vivo positive/negative regulators of p53 could be used to modulate susceptibility of tumor cells to complement lysis in chemotherapy.