DNA damage down-regulates ΔNp63α and induces apoptosis independent of wild type p53
DNA damage down-regulates ΔNp63α and induces apoptosis independent of wild type p53
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DOI：
10.1016/j.bbrc.2012.05.126
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发表时间：
2012-06-29
影响因子：
3.1
通讯作者：
Zhang, Yujun
中科院分区：
文献类型：
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作者：
Li, Xiaorong;Chen, Jing;Zhang, Yujun
肿瘤抑制因子p53在细胞应激（包括DNA损伤）时的细胞生长停滞和凋亡中起关键作用。越来越多的证据表明，p53的同源物p63蛋白在某些情况下也参与细胞凋亡。在这项研究中，我们发现用DNA损伤剂处理导致Delta Np63 α下调，并诱导携带突变型p53的FaDu和HaCat细胞凋亡。进一步的研究表明，DNA损伤降低了Delta Np63 α的稳态mRNA水平，但对其蛋白质稳定性影响不大。此外，内源性Δ Np63 α的敲低直接诱导细胞凋亡并使细胞对DNA损伤敏感，而Δ Np63 α的外源性表达部分赋予细胞对DNA损伤的抗性。总之，这些数据表明，DNA损伤下调Δ Np63 α，这可能直接有助于DNA损伤诱导的细胞凋亡。(C)2012 Elsevier Inc. All rights reserved.
The tumor suppressor p53 is pivotal in cell growth arrest and apoptosis upon cellular stresses including DNA damage. Mounting evidence indicates that p63 proteins, which are homologs of p53, are also involved in apoptosis under certain circumstances. In this study, we found that treatment with DNA damage agents leads to down-regulation of Delta Np63 alpha and induces apoptosis in FaDu and HaCat cells carrying mutant p53. Further study shows that DNA damage reduces steady-state mRNA level of Delta Np63 alpha, but has little effect on its protein stability. In addition, knockdown of endogenous Delta Np63 alpha directly induces apoptosis and sensitizes cells to DNA damage, while exogenous expression of Delta Np63 alpha partially confers cellular resistance to DNA damage. Together, these data suggest that DNA damage down-regulates Delta Np63 alpha, which may directly contribute to DNA damage-induced apoptosis. (C) 2012 Elsevier Inc. All rights reserved.