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- Title
Isoform specific phosphorylation of p53 by protein kinase CK1.
- Authors
Venerando, Andrea; Marin, Oriano; Cozza, Giorgio; Bustos, Victor H.; Sarno, Stefania; Pinna, Lorenzo Alberto
- 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.
- Subjects
PROTEIN kinases; THIAMIN pyrophosphate; P53 protein; PHOSPHORYLATION; MOLECULAR genetics
- Publication
Cellular & Molecular Life Sciences, 2010, Vol 67, Issue 7, p1105
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-009-0236-7