title: Identification of two serine residues important for p53 DNA binding and protein stability.
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.
authors.affiliation: Department of Biochemistry, University of California, Riverside, CA 92521, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Guoxia
authors.initials: G
authors.lastname: Liu
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012694:Serine / Q000032:analysis* / Q000502:physiology; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D012694:Serine; D004247:DNA; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2