title: Isoform specific phosphorylation of p53 by protein kinase CK1.
abstract: The ability of three isoforms of protein kinase CK1 (alpha, gamma(1), and delta) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide reproducing its 1-28 sequence. Both substrates are readily phosphoylated by CK1delta and CK1alpha, but not by the gamma isoform. Affinity of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K (m) 0.82 muM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1 is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and on a remote docking site mapped to the K(221)RQK(224) loop according to modeling and mutational analysis.
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Via G. Orus, 2, 35129, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Venerando
authors.forename: Oriano
authors.initials: O
authors.lastname: Marin
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cozza
authors.forename: Victor H
authors.initials: VH
authors.lastname: Bustos
authors.forename: Stefania
authors.initials: S
authors.lastname: Sarno
authors.forename: Lorenzo Alberto
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D047389:Casein Kinase I / Q000737:chemistry / Q000378:metabolism*; D048128:Casein Kinase Ialpha / Q000737:chemistry / Q000378:metabolism*; D048148:Casein Kinase Idelta / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; D047389:Casein Kinase I; D048128:Casein Kinase Ialpha; D048148:Casein Kinase Idelta