Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Binding Sites
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Cell Line
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Cell Line, Transformed
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DNA Mutational Analysis
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DNA-Binding Proteins / metabolism
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Feedback
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Fibroblasts
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Gene Expression Regulation, Neoplastic*
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Homeostasis
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Mice
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Molecular Sequence Data
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Mutation
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Neoplasm Proteins / genetics*
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Nuclear Proteins*
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Promoter Regions, Genetic
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Protein Binding
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Proto-Oncogene Proteins c-mdm2
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Proto-Oncogene Proteins*
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RNA, Messenger / metabolism
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Rats
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Temperature
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Transcription Factors / genetics
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Transcription, Genetic
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Transcriptional Activation*
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / physiology
Substances
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DNA-Binding Proteins
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Neoplasm Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Transcription Factors
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Tumor Suppressor Protein p53
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Mdm2 protein, mouse
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Mdm2 protein, rat
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Proto-Oncogene Proteins c-mdm2