Mitochondrial p53 levels parallel total p53 levels independent of stress response in human colorectal carcinoma and glioblastoma cells.
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.
Mahyar-Roemer
Mojgan
M
Internal Medicine IV, Bldg. 40, University of Saarland Medical School, Homburg/Saar 66421, Germany.
Fritzsche
Claudia
C
Wagner
Sascha
S
Laue
Michael
M
Roemer
Klaus
K
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000494:pharmacology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D005472:Fluorouracil