Role of p53 tumor suppressor in ageing: regulation of transient cell cycle arrest and terminal senescence
Wesierska-Gadek, J.; Wojciechowski, J.; Ranftler, C.; Schmid, G.
Journal of Physiology and Pharmacology An Official Journal of the Polish Physiological Society 56(1): 15-28
2005
ISSN/ISBN: 0867-5910 PMID: 15795472 Document Number: 593016
In this study we investigated the function of p53 as a regulator of cell cycle progression in cycling and senescent cells. Using the conditional temperature-sensitive (ts) mutant we could prevent the detrimental effect of constitutive expression of high levels of wt p53 protein. High levels of wt p53 inhibited cell proliferation by blocking the cells to progress from G(1) to S phase of the cell cycle. Flow cytometric analysis revelaed a maintenance of G(1) cell population for a longer time depending on the prolonged expression of wt p53 protein. The p53 mediated inhibition of cell proliferation and of the cycle was reversible. However, a spontaneous increase of wt p53 occurring in ageing normal human MRC-5 fibroblasts was associated with irreversible reduction of proliferative potential. The accumulation of G(1) cells was detected by flow cytometry. By the measurement of DNA content it is not possible to discriminate between cells arrested in G(1) and G(0)phase, therefore, the expression of G(1) markers was determined. Analysis of the expression of distinct cell cycle regulators revealed that quiescent MRC-5 cells were in G(0) phase. Our results indicate that cell cycle arrest occurring in senescent cells is associated with the G(0) transition.