DNA damage induces expression of WWP1 to target ΔNp63α to degradation.
DNA damage induces expression of WWP1 to target ΔNp63α to degradation.
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DNA 损伤诱导 WWP1 表达以靶向 ΔNp63α 降解
DOI：
10.1371/journal.pone.0176142
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Chen J;Shi H;Chen Y;Fan S;Liu D;Li C
Δ Np 63 α在细胞存活和增殖中起关键作用。所以它的表达总是在细胞中受到严格控制。我们先前报道了DNA损伤下调FaDu和HaCat细胞中Δ Np 63 α的转录，这有助于细胞凋亡。在本研究中，我们发现DNA损伤通过促进Δ Np 63 α在MDA-MB-231和MCF 10A等细胞系中的蛋白酶体降解而诱导Δ Np 63 α的下调。进一步的研究表明，WWP 1的转录受到这些细胞中DNA损伤的刺激。敲低WWP 1可消除DNA损伤诱导的Δ Np 63 α下调，并部分挽救细胞凋亡。有趣的是，DNA损伤可能通过不同的机制在不同的细胞类型中刺激WWP 1：它在MCF 10A和HEK 293细胞中以p53依赖性方式上调WWP 1的转录，而miR-452可能参与DNA损伤诱导的MDA-MB-231细胞中WWP 1的上调。我们的研究证明了一种新的途径，调节Δ Np 63 α细胞对化疗药物的反应。
ΔNp63αplays key roles in cell survival and proliferation. So its expression is always tightly controlled in cells. We previously reported that DNA damage down-regulates transcription of ΔNp63αin FaDu and HaCat cells, which contributes to cell apoptosis. In the present study, we found that DNA damage induces down-regulation of ΔNp63αvia facilitating its proteasomal degradation in cell lines such as MDA-MB-231 and MCF10A. Further investigation revealed that transcription of WWP1 is stimulated by DNA damage in these cells. Knock-down of WWP1 abrogates DNA damage-induced down-regulation of ΔNp63αand partially rescues cell apoptosis. Interestingly, DNA damage may stimulate WWP1 through different mechanisms in different cell types: it up-regulates transcription of WWP1 in a p53-dependent manner in MCF10A and HEK293 cells, while miR-452 may be involved in DNA damage-induced up-regulation of WWP1 in MDA-MB-231 cells. Our study demonstrates a novel pathway which regulates ΔNp63αupon cellular response to chemotherapeutic agents.