title: Crosstalk between site-specific modifications on p53 and histone H3.
abstract: Previously, we have observed a link between p53 expression and histone H3 post-translational modifications. Here, we ask if specific post-translational modifications of p53 impact upon histone H3 modifications in a selective manner. We have also screened for internal co-operative effects within the repertoire of p53 modifications. Exogenous p53 constructs were expressed in HCT116 p53-/- cells. Four mutant p53 constructs were used, with single 'phosphorylation' mutations at serines 15 and 37 (S15A, S15D, S37A and S37D) and compared with exogenously expressed wild-type p53. The results showed that the replacement of serine 15 with either alanine (S15A) or aspartic acid (S15D) induced phosphorylation at S33P, S37P and S46P. In contrast, phosphorylation mutants p53(S37A) and p53(S37D) were not phosphorylated on S33. S46 phosphorylation appeared specifically enhanced by p53(S37D) relative to p53(S37A). Distal induction of S392 phosphorylation was observed for each of the p53 N-terminal phosphorylation mutants. Analysis of endogenous histone H3 (from the transfected cells) revealed loss of di-methylated K9 following expression of wild type and mutant p53 constructs. Expression of p53 (S15A), (S15D) and (S37A) selectively induced acetylation at K9 and K14. In contrast, wt p53 and p53(S37D) had no effect upon K9 or K14 acetylation. K18 acetylation status was unaffected throughout.
authors: YCR p53 Research Group, Department of Biology, University of York, York, UK. ljw7@york.ac.uk
authors: L J
authors: LJ
authors: Warnock
authors: R
authors: R
authors: Adamson
authors: C J
authors: CJ
authors: Lynch
authors: J
authors: J
authors: Milner
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D045325:HCT116 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D012694:Serine