characterization of the p53 response to oncogene-induced senescence表征的p53应对oncogene-induced衰老.pdfVIP

Characterization of the p53 Response to Oncogene- Induced Senescence 1. 2. 1. 1 1 2 Lidia Ruiz , Magali Traskine , Irene Ferrer , Estrella Castro , Juan F. M. Leal , Marcelline Kaufman , Amancio Carnero1* ´ ´ 1 Experimental Therapeutics Programme, Centro Nacional De Investigaciones Oncologicas (CNIO), Madrid, Spain, 2 Unit of Theoretical and Computational Biology, Faculte ´ des Sciences, Universite Libre de Bruxelles (U.L.B.), Bruxelles, Belgium Abstract 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