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Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells

Oncogene volume 23, pages 6226–6236 (2004)Cite this article

Abstract

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 modifications. Thus, cell lines exist in which the mitochondrial p53 levels parallel total levels independent of apoptosis.

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Acknowledgements

We thank Bert Vogelstein, Johns Hopkins University, Baltimore, USA for the cell lines HCT116, HCT116 p53−/− and HCT116 p21−/−; we are also grateful to Erwin Van Meir, Emory University, Atlanta, USA for the cell line LN-Z308 p53wt. Finally, we thank Gabi Kiefer, Institute of Anatomy, for excellent technical assistance with electron microscopy. This work was supported by the German Research Foundation (DFG) Grant RO 1205/5-1 to KR.

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  1. Internal Medicine IV, Bldg. 40, University of Saarland Medical School, Homburg/Saar, 66421, Germany

    Mojgan Mahyar-Roemer

  2. Department of Virology, Bldg. 47, University of Saarland Medical School, Homburg/Saar, 66421, Germany

    Claudia Fritzsche, Sascha Wagner & Klaus Roemer

  3. Department of Anatomy and Cell Biology, Center for Electron Microscopy, Bldg. 61, University of Saarland Medical School, Homburg/Saar, 66421, Germany

    Michael Laue

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  1. Mojgan Mahyar-Roemer
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Correspondence to Klaus Roemer.

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Mahyar-Roemer, M., Fritzsche, C., Wagner, S. et al. Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells. Oncogene 23, 6226–6236 (2004). https://doi.org/10.1038/sj.onc.1207637

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