title: p53 Oligomerization is essential for its C-terminal lysine acetylation.
abstract: Acetylation of multiple lysine residues in the p53 plays critical roles in the protein stability and transcriptional activity of p53. To better understand how p53 acetylation is regulated, we generated a number of p53 mutants and examined acetylation of each mutant in transfected cells. We found that p53 mutants that are defective in tetramer formation are also defective in C-terminal lysine residue acetylation. Consistently, we found that several cancer-derived p53 mutants that bear mutations in the tetramerization domain cannot form oligomers and are defective in C-terminal lysine acetylation, and these mutants are inactive in p21 transactivation. We demonstrated that the acetyltransferase p300 interacts with and promotes acetylation of wild-type p53 but not with any of the artificially generated or human cancer-derived p53 mutants that are defective in oligomerization. These results, combined with a computer-aided crystal structure analysis, suggest a model in which p53 oligomerization precedes its acetylation by providing docking sites for acetyltransferases.
authors.affiliation: Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina 27599-7512, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Itahana
authors.forename: Hengming
authors.initials: H
authors.lastname: Ke
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D055550:Protein Stability; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C495901:TP53 protein, human