The p53-mdm-2 autoregulatory feedback loop.
The p53 protein can bind to a set of specific DNA sequences, and this may activate the transcription of genes adjacent to these DNA elements. The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm-2 gene can be regulated by the level of wild-type p53 protein. The mdm-2 protein, in turn, can complex with p53 and decrease its ability to act as a positive transcription factor at the mdm-2 gene-responsive element. In this way, the mdm-2 gene is autoregulated. The p53 protein regulates the mdm-2 gene at the level of transcription, and the mdm-2 protein regulates the p53 protein at the level of its activity. This creates a feedback loop that regulates both the activity of the p53 protein and the expression of the mdm-2 gene.
Wu
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Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
Bayle
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Olson
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Levine
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005246:Feedback; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2