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Irradiation-induced translocation of p53 to mitochondria in the absence of apoptosis

Item Type:Article
Title:Irradiation-induced translocation of p53 to mitochondria in the absence of apoptosis
Creators Name:Essmann, F. and Pohlmann, S. and Gillissen, B. and Daniel, P.T. and Schulze-Osthoff, K. and Jaenicke, R.U.
Abstract:The tumor suppressor protein p53 promotes apoptosis in response to death stimuli by transactivation of target genes and by transcription-independent mechanisms. Recently, it was shown that during apoptosis p53 can specifically translocate to mitochondria, where it physically interacts with and inactivates prosurvival Bcl-2 proteins. In the present study, we therefore investigated the role of mitochondrial translocation of p53 for the stress response of tumor cells. In various cell lines, DNA damage induced by either ionizing irradiation or topoisomerase inhibitors triggered a robust translocation of a fraction of p53 to mitochondria to a similar extent. Nevertheless, the cells succumbed to apoptosis only in response to topoisomerase inhibitors, but remained resistant to apoptosis induced by ionizing radiation. Irradiated cells became senescent, although irradiation triggered a functional p53 response and induced expression of p21, Bax, and Puma. Interestingly, even the targeted expression of p53 to mitochondria was insufficient to launch apoptosis, whereas overexpression of wild-type p53 induced Bax activation and apoptotic alterations. Together, these results suggest that, in contrast to previous reports, mitochondrial translocation of p53 does not per se lead to cell death and that this might constitute a mechanism that contributes to the resistance of tumor cells to ionizing radiation-induced apoptosis.
Keywords:Apoptosis, Apoptosis Regulatory Proteins, Breast Neoplasms, Colonic Neoplasms, Cultured Tumor Cells, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, Enzyme Inhibitors, Fibroblasts, Ionizing Radiation, Mitochondria, Protein Transport, Proto-Oncogene Proteins, Small Interfering RNA, Topoisomerase I Inhibitors, Tumor Suppressor Protein p53, bcl-2-Associated X Protein, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:280
Number:44
Page Range:37169-37177
Date:4 November 2005
Official Publication:https://doi.org/10.1074/jbc.M502052200
PubMed:View item in PubMed

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