Abstract
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-alpha, -delta, -epsilon or -zeta, we showed a differential regulation of p53 activity and phosphorylation state by PKC isoforms. Whereas PKC-alpha reduced the p53-induced yeast growth inhibition and cell cycle arrest, PKC-delta and -epsilon enhanced the p53 activity through p53 phosphorylation, and PKC-zeta had no effect on p53. This work identified positive and negative p53 regulators which represent promising pharmacological targets in anti-cancer therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cattle
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Cell Cycle
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Cell Division
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Flow Cytometry
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Humans
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Mice
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Phosphorylation
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Protein Kinase C / genetics
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Protein Kinase C / metabolism*
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Protein Kinase C-alpha / genetics
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Protein Kinase C-alpha / metabolism*
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Protein Kinase C-delta / genetics
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Protein Kinase C-delta / metabolism*
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Protein Kinase C-epsilon / genetics
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Protein Kinase C-epsilon / metabolism*
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Rats
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Transformation, Genetic
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Yeasts / cytology
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Yeasts / genetics
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Yeasts / growth & development
Substances
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Tumor Suppressor Protein p53
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protein kinase C zeta
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Protein Kinase C
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Protein Kinase C-alpha
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Protein Kinase C-delta
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Protein Kinase C-epsilon