Monday, 8 May 2017

p53

It «(...) is one of the most commonly mutated tumor suppressors whose function is to regulate genes that control both cell cycle checkpoints and (...) apoptosis. Consequently, activation of p53 after irradiation can lead either to a block in proliferation or directly to cell death. (...) in unstressed normal cells, p53 is made continuously but is degraded and thus non-functional. Following DNA [deoxyribonucleic acid] damage, ATM [ataxia telangiectasia mutated] phosphorylates both p53 and MDM2 [murine double minute 2]. These events destabilize the p53-MDM2 interaction, and (...) p53 protein is no longer degraded. In addition to this stabilization, direct phosphorylation of p53 by ATM leads to its activation as a transcription factor and thus the upregulation of its many target genes [1].»
«Cells irradiated in the G1 phase are influenced by the action of p53. ATM protein is activated by double-strand DNA breaks and phosphorylates both MDM2 and p53. This leads to stabilization and activation of p53, which induces genes that can promote apoptosis (Bax [Bcl-2-associated X], Puma [p53 upregulated modulator of apoptosis]) and induces checkpoints. (...) cells are blocked at the G1/S border [1].»
Is has «(...) a mass of 53 kDa (hence its name); p53 protein is normally induced in cells having undergone DNA damage, (...); its principal effects are to stop the cell cycle and prevent the cell from undergoing mitosis; thus, DNA mutations/damage can either be repaired or a damaged cell can be eliminated from the organism, for example via apoptosis. p53 is also known as the guardian of the genome [2].»
Bibliographic references:
[1] Joiner, M. and Kogel, A. (2009). Basic clinical radiobiology. 1st ed. Boca Raton, Florida: CRC Press, p.17.
[2] Tortora, G., Bergmann, L., Lindh, M., Cervantes-Ruiperez, A., Dziadziuszko, R., Eckhardt, S., Lenz, H., Normanno, N., Perez, D., Scarpa, A., Syrigos, K., Tabernero, J. and Troiani, T. (2014). ESMO glossary in molecular biology of cancer. Viganello-Lugano, Switzerland: European Society for Medical Oncology, p.117.