Cellular and Molecular Life Sciences

, Volume 67, Issue 7, pp 1105–1118 | Cite as

Isoform specific phosphorylation of p53 by protein kinase CK1

  • Andrea Venerando
  • Oriano Marin
  • Giorgio Cozza
  • Victor H. Bustos
  • Stefania Sarno
  • Lorenzo Alberto Pinna
Research Article

Abstract

The ability of three isoforms of protein kinase CK1 (α, γ1, and δ) 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 CK1δ and CK1α, but not by the γ isoform. Affinity of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (Km 0.82 μM 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 K221RQK224 loop according to modeling and mutational analysis.

Keywords

Casein kinase 1 CK1 CKI p53 phosphorylation p53 Ser20 

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Andrea Venerando
    • 1
    • 2
  • Oriano Marin
    • 1
    • 2
  • Giorgio Cozza
    • 2
  • Victor H. Bustos
    • 1
    • 3
  • Stefania Sarno
    • 1
    • 2
  • Lorenzo Alberto Pinna
    • 1
    • 2
  1. 1.Venetian Institute of Molecular Medicine (VIMM)PadovaItaly
  2. 2.Department of Biological ChemistryUniversity of PadovaPadovaItaly
  3. 3.Laboratory of Molecular and Cellular NeuroscienceThe Rockefeller UniversityNew YorkUSA

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