title: Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15.
abstract: p53 is a potent transcription factor which is regulated by sequential multisite phosphorylation and acetylation. In this paper, we identify threonine 18 of p53, a key site in regulating the interaction between p53 and its regulatory partner MDM2, as a novel site phosphorylated in vitro by purified recombinant casein kinase 1 (CK1) delta. Strikingly, phosphorylation of threonine 18 is dependent upon prior phosphorylation of serine 15. These data highlight an additional and physiologically important target residue for CK1 in p53 and suggest a potential mechanism by which sequential modification of a pivotal N-terminal residue in p53 may occur following stress-activated modification of serine 15.
authors.affiliation: Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: N
authors.initials: N
authors.lastname: Dumaz
authors.forename: D M
authors.initials: DM
authors.lastname: Milne
authors.forename: D W
authors.initials: DW
authors.lastname: Meek
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D047388:Casein Kinases; D004249:DNA Damage; D005982:Glutathione Transferase / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment; D012694:Serine / Q000737:chemistry; D013379:Substrate Specificity; D013912:Threonine / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D013912:Threonine; D012694:Serine; D005982:Glutathione Transferase; D011494:Protein Kinases; D047388:Casein Kinases