ON THE REGULATION OF THE P53 TUMOR-SUPPRESSOR, AND ITS ROLE IN THE CELLULAR-RESPONSE TO DNA-DAMAGE

The p53 gene is required for the normal apoptotic response of mammalia n cells to DNA damage caused by ionizing radiation and DNA damaging dr ugs. DNA damage results in the accumulation of biologically active p53 . This response is potentially lethal and is therefore highly regulate d. By using both biochemical and cell biological approaches a number o f discrete control pathways have been identified. These include analys is of cellular and viral proteins that bind to p53 to inactivate its f unction, the discovery of cells with defects in the p53 activation pat hway and the analysis of an allosteric regulation of p53 function cont rolled by phosphorylation.