دورية أكاديمية
Characterization of the p53 Response to Oncogene-Induced Senescence
| العنوان: | Characterization of the p53 Response to Oncogene-Induced Senescence |
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| المؤلفون: | Ruiz, Lidia, Traskine, Magali, Ferrer, Irene, Castro, Estrella, Leal, Juan F. M., Kaufman, Marcelline, Carnero, Amancio |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2008 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Catalytic domains, Cell aging, Cell proliferation, Heterozygote, Least-squares analysis, Phenotype, Protein phosphatase 1, Tumor suppressor protein p53 |
| الوصف: | 14 páginas, 7 figuras, 2 tablas. ; Background P53 activation can trigger various outcomes, among them reversible growth arrest or cellular senescence. It is a live debate whether these outcomes are influenced by quantitative or qualitative mechanisms. Furthermore, the relative contribution of p53 to Ras-induced senescence is also matter of controversy. Methodology/Principal Findings This study compared situations in which different signals drove senescence with increasing levels of p53 activation. The study revealed that the levels of p53 activation do not determine the outcome of the response. This is further confirmed by the clustering of transcriptional patterns into two broad groups: p53-activated or p53-inactivated, i.e., growth and cellular arrest/senescence. Furthermore, while p53-dependent transcription decreases after 24 hrs in the presence of active p53, senescence continues. Maintaining cells in the arrested state for long periods does not switch reversible arrest to cellular senescence. Together, these data suggest that a Ras-dependent, p53-independent, second signal is necessary to induce senescence. This study tested whether PPP1CA (the catalytic subunit of PP1α), recently identified as contributing to Ras-induced senescence, might be this second signal. PPP1CA is induced by Ras; its inactivation inhibits Ras-induced senescence, presumably by inhibiting pRb dephosphorylation. Finally, PPP1CA seems to strongly co-localize with pRb only during senescence. Conclusions The levels of p53 activation do not determine the outcome of the response. Rather, p53 activity seems to act as a necessary but not sufficient condition for senescence to arise. Maintaining cells in the arrested state for long periods does not switch reversible arrest to cellular senescence. PPP1CA is induced by Ras; its inactivation inhibits Ras-induced senescence, presumably by inhibiting pRb dephosphorylation. Finally, PPP1CA seems to strongly co-localize with pRb only during senescence, suggesting that PP1α activation during ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | Publisher’s version; http://dx.doi.org/10.1371/journal.pone.0003230Test; PLoS ONE 3(9): e3230 (2008); PMID:18800172; PMC2535567; http://hdl.handle.net/10261/38832Test |
| DOI: | 10.1371/journal.pone.0003230 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0003230Test http://hdl.handle.net/10261/38832Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.E8066419 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0003230 |