DNA damage-induced inhibition of securin expression is mediated by p53
DNA damage-induced inhibition of securin expression is mediated by p53
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DOI：
10.1074/jbc.m203793200
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发表时间：
2003-01-03
影响因子：
4.8
通讯作者：
Zhang, X
中科院分区：
文献类型：
--
作者：
Zhou, YL;Mehta, KR;Zhang, X
抑癌基因P53主要通过调节其下游靶基因的表达来诱导细胞对DNA损伤的反应。人类Securin是一种后期抑制物，通过抑制分离酶活性来防止染色体过早分离。它也被认为是人类脑下垂体肿瘤转化基因pttg的产物，pttg是一种原癌基因。在此，我们报道了在DNA损伤药物阿霉素和博莱霉素处理的细胞中，人类Securin的表达被抑制。这种抑制需要有功能的P53。对人Securin启动子的分析表明，Sp1和NF-Y的DNA结合位点都是激活Securin表达所必需的；然而，只有NF-Y位点对于P53的抑制是必不可少的。我们的研究表明，Securin是一个P53靶基因，可能在P53介导的细胞对DNA损伤的反应中发挥作用。
Tumor suppressor p53 induces the cellular response to DNA damage mainly by regulating expression of its downstream target genes. The human securin is an anaphase inhibitor, preventing premature chromosome separation through inhibition of separase activity. It is also known as the product of the human pituitary tumor-transforming gene, pttg, a proto-oncogene. Here we report that the expression of human securin is suppressed in cells treated with the DNA-damaging drugs doxorubicin and bleomycin. This suppression requires functional p53. Analysis of the human securin promoter reveals that DNA-binding sites for Sp1 and NF-Y are both required for activation of securin expression; however, only the NF-Y site is essential for the suppression by p53. Our study indicates that securin is a p53 target gene and may play a role in p53-mediated cellular response to DNA damage.