Papillomavirus E2 induces p53-independent apoptosis in HeLa cells
Papillomavirus E2 induces p53-independent apoptosis in HeLa cells
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DOI：
10.1038/sj.onc.1202818
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发表时间：
1999-08-12
期刊：
影响因子：
8
通讯作者：
Thierry, F
中科院分区：
文献类型：
--
作者：
Desaintes, C;Goyat, S;Thierry, F
我们之前的研究表明，HeLa细胞中乳头瘤病毒E2蛋白的表达可诱导p53积累，导致细胞周期阻滞和凋亡，与生长阻滞相反，凋亡的发生与p53转录活性的增加无关，在本研究中，我们进行了生化和遗传学实验，以确定et诱导的凋亡是否独立于p53诱导。我们发现E2不会改变Bar的转录，Bar是一种已知的p53激活的细胞死亡诱导剂。凋亡细胞死亡的时间过程早于p53诱导数小时。过表达HPV18 E6癌基因可阻止e2介导的p53积累，但不改变细胞死亡率。最后，hpv18e2反活化结构域的点突变体诱导凋亡，尽管它们不能诱导p53的高积累或细胞周期阻滞。此外，从这些突变体获得的结果表明，E2的转录激活和复制功能对于诱导细胞死亡是不可或缺的。这些观察结果表明e2诱导的细胞凋亡是一个早期事件，独立于p53积累，与下游p53依赖的转录事件无关。
We have previously shown that expression of the papillomavirus E2 protein in HeLa cells induces p53 accumulation and causes both cell cycle arrest and apoptosis, In contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity, In the present study, we conducted biochemical and genetic experiments in order to determine whether Et-induced apoptosis was independent of p53 induction. We showed that E2 did not alter the transcription of Bar, a known p53-activated cell death inducer. The time course of apoptotic cell death preceded p53 induction by several hours. Overexpression of the HPV18 E6 oncogene prevented E2-mediated p53 accumulation, but did not alter the rate of cell death. Finally, point mutants of the HPV18 E2 transactivation domain induced apoptosis, although they were unable to induce high p53 accumulation or cell cycle arrest. In addition, the results obtained with these mutants indicated that both transcriptional activation and replication functions of E2 were dispensable for the induction of cell death. These observations show that E2-induced apoptosis is an early event, independent of p53 accumulation and unrelated to downstream p53-dependent transcriptional events.