Abstract
In MCF-7 cells, TNFα induces a G1 arrest with an increased expression of p21/Waf1, an activation of NF-κB and an accumulation of p53. NF-κB and p53 are two transcriptional factors known to activate p21/Waf1 gene expression. Here we show that p53 inhibition has no effect on p21/Waf1 mRNA accumulation following TNFα treatment. In contrast, inactivation of NF-κB inhibits p21/Waf1 expression without affecting G1 arrest. The fact that p21/Waf1 gene expression is still stimulated when p53 is inactivated strongly suggests that TNFα induces accumulation of an inactive form of p53 protein. This assumption was further supported by the following observations: (i) the p53 DNA-binding activity to its consensus sequence was not stimulated following TNFα treatment, (ii) phosphorylation at Ser-15, -20 or -392 was not detected in response to TNFα, (iii) the transcription rate of Ddb2, another p53 target gene, was not stimulated by TNFα. Finally, the accumulation of p53 in the nuclei of TNFα-treated MCF-7 cells was concomitant with an increase in p53 mRNA level, suggesting a regulation at the transcription level.
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Abbreviations
- HPV:
-
human papilloma virus
- NaSal:
-
sodium salicylate
- p53-DD:
-
p53 dominant-negative
- SOD2:
-
superoxide dismutase 2
- TNFα:
-
tumour necrosis factor-alpha
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Acknowledgements
We are grateful to S Chouaib for providing MCF-7/MAD1904 and MCF-7/E6 cell lines and to D Lane for providing DO-7 hybridoma cells. We wish to thank P May and JC Lelong for critical reading of the manuscript. This work was supported by grant FMRX-CT97-0153 from the European Commission and by a grant from EDF. P Drané was supported by a fellowship from CEA and from EDF.
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Drané, P., Leblanc, V., Miro-Mur, F. et al. Accumulation of an inactive form of p53 protein in cells treated with TNFα. Cell Death Differ 9, 527–537 (2002). https://doi.org/10.1038/sj.cdd.4400983
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DOI: https://doi.org/10.1038/sj.cdd.4400983
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