THE EMERGING PICTURE OF P53

1. The cellular phosphoprotein p53 is a negative regulator of the cell growth. A great majority of human malignancies expresses a mutated p53 that represents an oncogenic version of the protein. 2. However, in the meantime many tumors were identified containing a p53 protein without any mutation. Here also other events than genomic alterations of p53 might be implicated in the process of cell transformation. 3. The expression of wild-type or mutant conformation is not exclusively defined by the p53 DNA sequence but also influenced by the subcellular environment and the interaction of cellular proteins with p53. 4. In particular, the mdm-2 gene product appears to be an important partner of p53 somehow involved in these complex regulatory processes. 5. Recent findings supported a role for p53 in transcriptional regulation, perhaps by reducing the expression of genes that are needed for ongoing cell proliferation. 6. This property may be based upon the ability of p53 to bind DNA as well as different proteins from viral or cellular origin. 7. Especially transcription factors or further cellular proteins connected in any way with the regulation of cell proliferation are possible candidates. 8. Thus, it is not surprising that p53 is implicated in the regulation of the cell cycle and in the decision of a cell to replicate DNA or to go into apoptosis.