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 human tumors, and its product inactivates the p53 tumor suppressor protein. MDM2 forms an autoregulatory loop with p53, because the mdm2 gene contains a promoter that is responsive to p53. Synthesis of MDM2 protein increases in a p53-dependent manner in response to DNA-damaging agents such as UV light. Although this increase likely results from enhanced 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 not induced. The amount of the mdm2 transcript does not parallel the ability of p53 to bind DNA, indicating that transcription is regulated at a step distinct from activation of the DNA-binding function of p53.
Saucedo
L J
LJ
Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
Carstens
B P
BP
Seavey
S E
SE
Albee
L D
LD
Perry
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA; C497207:Mdm2 protein, mouse; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2