PML regulates p53 acetylation and premature senescence induced by oncogenic Ras Journal Article
| Authors: | Pearson, M.; Carbone, R.; Sebastiani, C.; Cloce, M.; Fagloll, M.; Saito, S.; Higashimoto, Y.; Appella, E.; Minucci, S.; Pandolfi, P. P.; Pellcci, P. G. |
| Article Title: | PML regulates p53 acetylation and premature senescence induced by oncogenic Ras |
| Abstract: | The tumour, suppressor p53 induces cellular senescence in response to oncogenic signals. p53 activity is modulated by protein stability and post- translational modification, including phosphorylation and acetylation. The mechanism of p53 activation by oncogenes remains largely unknown. Here we report that the turnout suppressor PML regulates the p53 response to oncogenic signals. We found that oncogenic Ras upregulates PML expression, and overexpression of PML induces senescence in a p53-dependent manner, p53 is acetylated at lysine 382 upon Ras expression, an event that is essential for its biological function. Ras induces relocalization of p53 and the CBP acetyltransferase within the PML nuclear bodies and induces the formation of a trimeric p53-PML-CBP complex. Lastly, Ras-induced p53 acetylation, p53-CBP complex stabilization and senescence are lost in PML fibroblasts. Our data establish a link between PML and p53 and indicate that integrity of the PML bodies is required for p53 acetylation and senescence upon oncogene expression. |
| Keywords: | signal transduction; controlled study; nonhuman; protein localization; animal cell; mouse; animals; mice; complex formation; gene overexpression; gene expression; embryo; neoplasm proteins; protein p53; animalia; transcription factors; nuclear proteins; tumor suppressor gene; genetic transfection; tumor suppressor proteins; fibroblast; tumor suppressor protein p53; gene control; cell nucleus; gene induction; senescence; genes, ras; up-regulation; cell aging; oncogene ras; lysine; acyltransferase; acetylation; humans; priority journal; article |
| Journal Title: | Nature |
| Volume: | 406 |
| Issue: | 6792 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2000-07-13 |
| Start Page: | 207 |
| End Page: | 210 |
| Language: | English |
| DOI: | 10.1038/35018127 |
| PUBMED: | 10910364 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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