AI Article Synopsis
- The study investigates how three CK1 protein isoforms (alpha, gamma(1), and delta) phosphorylate the N-terminal region of the p53 protein.
- CK1alpha and CK1delta effectively phosphorylate p53, particularly targeting serine 20 (S20), but CK1gamma does not participate in this process.
- The research reveals that full-length p53 has a significantly higher affinity for CK1 compared to a synthetic peptide version and highlights a specific mechanism for phosphorylation that relies on both consensus sequences and the positioning of certain residues.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115815 | PMC |
| http://dx.doi.org/10.1007/s00018-009-0236-7 | DOI Listing |
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