Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells
Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells
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DOI：
10.1038/sj.onc.1207637
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发表时间：
2004-08-19
期刊：
影响因子：
8
通讯作者：
Roemer, K
中科院分区：
文献类型：
--
作者：
Mahyar-Roemer, M;Fritzsche, C;Roemer, K
p53可以通过诱导线粒体介导的细胞凋亡来消除受损细胞。最近的观察提供了强有力的证据表明，总p53易位到线粒体的一小部分，特别是在响应死亡刺激。出乎意料的是，突变型p53，这是在非应激细胞中的表达水平比野生型高得多，显然总是存在于线粒体，独立于凋亡信号。这促使我们问是否存在完整的p53依赖性凋亡和细胞周期阻滞途径的细胞系，其中野生型p53的线粒体定位，像突变体一样，是独立的死亡刺激，而是与总p53水平相关。在这里，我们的文件，人HCT 116结直肠癌细胞阿霉素或5-氟尿嘧啶（5 FU）治疗可以积累总p53到同样高的水平，和线粒体p53的比例水平，虽然只有5 FU治疗引起p53依赖性细胞凋亡。沿着相同的线，具有增加的基础p53水平的HCT 116衍生物和具有多西环素诱导的p53的胶质母细胞瘤细胞也显示成比例的线粒体p53水平，并且甚至未应激的HCT 116细胞也具有位于线粒体的一些p53。最后，线粒体和总p53表现出不同的翻译后修饰。阳离子。因此，存在线粒体p53水平平行于不依赖于凋亡的总水平的细胞系。
p53 can eliminate damaged cells through the induction of mitochondria-mediated apoptosis. Recent observations have provided strong evidence that a fraction of total p53 translocates to mitochondria specifically in response to a death stimulus. Unexpectedly, mutant p53, which is expressed at much higher levels than wild type in unstressed cells, is apparently always present at the mitochondria, independent of apoptotic signal. This prompted us to ask whether cell lines with intact p53-dependent apoptosis and cell cycle arrest pathways exist in which the mitochondrial localization of wild-type p53, like that of mutant, is independent of a death stimulus and instead, correlates with the total p53 levels. Here, we document that human HCT116 colorectal carcinoma cells treated with adriamycin or 5-fluorouracil (5FU) can accumulate total p53 to equally high levels, and mitochondrial p53 to proportionate levels, although only 5FU treatment provoked p53-dependent apoptosis. Along the same line, HCT116 derivatives with increased basal p53 levels, and glioblastoma cells with a doxycycline-inducible p53, also revealed proportionate mitochondrial p53 levels, and even unstressed HCT116 cells had some p53 located at the mitochondria. Finally, mitochondrial and total p53 showed distinct post-translational modi. cations. Thus, cell lines exist in which the mitochondrial p53 levels parallel total levels independent of apoptosis.