REGULATION OF TRANSCRIPTIONAL ACTIVATION OF MDM2 GENE BY P53 IN RESPONSE TO UV-RADIATION

The mdm2 oncogene is expressed at elevated levels in a variety of huma n tumors, and its product inactivates the p53 tumor suppressor protein , MDM2 forms an autoregulatory loop with p53, because the mdm2 gene co ntains a promoter that is responsive to p53, Synthesis of MDM2 protein increases in a p53-dependent manner in response to DNA-damaging agent s such as UV light. Although this increase likely results from enhance d transcription, the amount of MDM2 protein does not correspond to the amount of p53 protein in cells exposed to UV light, Here we show that the p53-specific internal promoter in the mdm2 gene is induced after exposure to UV light, whereas the upstream constitutive promoter is no t induced, The amount of the mdm2 transcript does not parallel the abi lity of p53 to bind DNA, indicating that transcription is regulated at a step distinct from activation of the DNA-binding function of p53.