Mammalian cell death model of p53 induced apoptosis

摘要

Although apoptosis is a physiological pathway to cell suicide that is critical to normal development and homeostasis, the mechanism of cell death has not been well elucidated because of the complicated multiple signal pathways involved. The p53 tumor suppressor gene is a transcriptional factor that induces cell cycle arrest and apoptosis and recognized as a central component of the apoptosis system. In this study, we try to establish the cell system in which apoptosis can be induced spontaneously by introducing temperature sensitive dominant negative p53 mutant into mammalian epithelial cell lines. Using this cell system the time-course of changes of the number of cells were evaluated from the onset of apoptosis cell death signal. After activating wild type p53, the number of cells continued to increase until around 18 hours, and began to decrease logarithmically rather than linearly. Based on molecular biological findings for p53-induced apoptosis, it can be estimated that once cell death signal is introduced, cell cycle arrest precedes apoptosis in the passage of cell death. These cell death model concerning apoptosis could be useful for further understanding of the life span of human beings.