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Differential regulation of p53 function by protein kinase C isoforms revealed by a yeast cell system
Author(s) -
Coutinho Isabel,
Pereira Gil,
Leão Mariana,
Gonçalves Jorge,
Côrte-Real Manuela,
Saraiva Lucília
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.10.030
Subject(s) - protein kinase c , gene isoform , phosphorylation , microbiology and biotechnology , yeast , biology , function (biology) , kinase , cell growth , signal transduction , cell cycle , biochemistry , chemistry , cell , gene
The complexity of the mammalian p53 pathway and protein kinase C (PKC) family has hampered the discrimination of the effect of PKC isoforms on p53 activity. Using yeasts co‐expressing the human wild‐type p53 and a mammalian PKC‐α, ‐δ, ‐ε or ‐ζ, we showed a differential regulation of p53 activity and phosphorylation state by PKC isoforms. Whereas PKC‐α reduced the p53‐induced yeast growth inhibition and cell cycle arrest, PKC‐δ and ‐ε enhanced the p53 activity through p53 phosphorylation, and PKC‐ζ had no effect on p53. This work identified positive and negative p53 regulators which represent promising pharmacological targets in anti‐cancer therapy.