Accumulation of an inactive form of p53 protein in cells treated with TNFα
| Autor: | P Drané, V Leblanc, R Saffroy, Evelyne May, F Miro-Mur, B Debuire |
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| Rok vydání: | 2002 |
| Předmět: |
Cell Nucleus
Cyclin-Dependent Kinase Inhibitor p21 Messenger RNA Tumor Necrosis Factor-alpha G1 Phase NF-kappa B Gene Expression RNA Cell Biology Biology Molecular biology Transcription (biology) Cyclins Gene expression Serine Tumor Cells Cultured Consensus sequence Humans Phosphorylation Tumor necrosis factor alpha RNA Messenger Tumor Suppressor Protein p53 Molecular Biology Transcription factor |
| Zdroj: | Cell Death & Differentiation. 9:527-537 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | In MCF-7 cells, TNF alpha induces a G1 arrest with an increased expression of p21/Waf1, an activation of NF-kappa B and an accumulation of p53. NF-kappa B 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 TNF alpha treatment. In contrast, inactivation of NF-kappa B 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 TNF alpha 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 TNF alpha treatment, (ii) phosphorylation at Ser-15, -20 or -392 was not detected in response to TNF alpha, (iii) the transcription rate of Ddb2, another p53 target gene, was not stimulated by TNF alpha. Finally, the accumulation of p53 in the nuclei of TNF alpha-treated MCF-7 cells was concomitant with an increase in p53 mRNA level, suggesting a regulation at the transcription level. |
| Databáze: | OpenAIRE |
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