Isoform specific phosphorylation of p53 by protein kinase CK1

Cell Mol Life Sci. 2010 Apr;67(7):1105-18. doi: 10.1007/s00018-009-0236-7. Epub 2009 Dec 30.

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Casein Kinase I / chemistry
  • Casein Kinase I / metabolism*
  • Casein Kinase Ialpha / chemistry
  • Casein Kinase Ialpha / metabolism*
  • Casein Kinase Idelta / chemistry
  • Casein Kinase Idelta / metabolism*
  • Computer Simulation
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*
  • Zebrafish Proteins / chemistry
  • Zebrafish Proteins / metabolism

Substances

  • Isoenzymes
  • Tumor Suppressor Protein p53
  • Zebrafish Proteins
  • Casein Kinase I
  • Casein Kinase Ialpha
  • Casein Kinase Idelta