Isoform specific phosphorylation of p53 by protein kinase CK1 |
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Authors: | Andrea Venerando Oriano Marin Giorgio Cozza Victor H. Bustos Stefania Sarno Lorenzo Alberto Pinna |
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Affiliation: | (1) Venetian Institute of Molecular Medicine (VIMM), Via G. Orus, 2, 35129 Padova, Italy;(2) Department of Biological Chemistry, University of Padova, Viale G. Colombo, 3, 35131 Padova, Italy;(3) Present address: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA; |
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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 (K m 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. |
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