Abstract
The p53 core DNA binding domain has been implied in Mdm2-mediated protein degradation. Here we show that the substitution of the serine residues 116 and 127 with alanine residues (S116/127A) has no effect on p53 DNA binding and protein stability. However, the substitution of the serine residues with the aspartic acid (S116/127D) abolished p53 DNA binding and led to protein stabilization. Importantly, we have shown that S116/127D exhibits a structural mutant conformation that results in a loss of p53-dependent transcription and Mdm2-mediated protein degradation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Cell Line
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DNA / metabolism*
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Humans
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Mice
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Nuclear Proteins*
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Protein Conformation
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-mdm2
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Serine / analysis*
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Serine / physiology
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Transcriptional Activation
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Tumor Suppressor Protein p53 / chemistry*
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Nuclear Proteins
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p53
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Serine
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DNA
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MDM2 protein, human
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2