Journal
FEBS LETTERS
Volume 583, Issue 22, Pages 3582-3588Publisher
WILEY
DOI: 10.1016/j.febslet.2009.10.030
Keywords
p53; Protein kinase C isoform; Cell growth; Cell cycle; p53 phosphorylation; Yeast
Funding
- REQUIMTE
- FCT [SFRH/BD/36066/2007]
- POCTI
- FEDER
- Universidade do Porto
- Fundação para a Ciência e a Tecnologia [SFRH/BD/36066/2007] Funding Source: FCT
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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. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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