Model of p53 Function

The p53 protein represents a control element that links progress in the cell cycle and smwival of a cell with the effect of genotoxic stress (especially DNA damage). 

As a reaction to DNA damage, the activated p53 protein may act at several points in the course of the cell cycle and bring this to a halt. The halt at the Gl/S phase transition is mediated by the inhibitor p21° in particular. A stop in the cell cycle at the G2/M transition and in mitosis may also be mediated by activated p53. 

The second important function of the p53 protein is initiation of apoptosis. This pathway involves induction of the Bax protein, which is a part of the apoptotic program of the cell. 

The intact network of p53 regulation helps to maintain the genomic integrity of the cell by eliminating damaged cells. This may take place by permanent arrest in the G1 phase, at the G2/M transition and in mitosis or by initiation of apoptosis. 

A selection of other tumor suppressor genes is summarized in Table 14.2. Interestingly, an enzyme of phosphatidyl-inositol metabolism has been also identified as a tumor suppressor. The PTEN tumor suppressor gene codes for a phospholipid phosphatase which specifically cleaves a phosphate from the second messenger phosphatidyl-inosi-tol-3,4,5-trisphosphate (PtdInsPj, see 6.6.2). and thus inactivates the messenger (review Maehama and Dixon, 1999).  

---