Differential regulation of p53 function by protein kinase C isoforms revealed by a yeast cell system

Coutinho, Isabel; Pereira, Gil; Leão, Mariana; Gonçalves, Jorge; Côrte-Real, Manuela; Saraiva, Lucília

doi:10.1016/j.febslet.2009.10.030

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Volume 583, Issue 22 , Pages 3582-3588, 19 November 2009

Differential regulation of p53 function by protein kinase C isoforms revealed by a yeast cell system

Edited by Varda Rotter

Isabel Coutinho
- Laboratório de Microbiologia, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal
Gil Pereira
- Laboratório de Microbiologia, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal
Mariana Leão
- Laboratório de Microbiologia, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal
Jorge Gonçalves
- Laboratório de Farmacologia, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal
Manuela Côrte-Real
- Centro de Biologia Molecular e Ambiental, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Lucília Saraiva
- Laboratório de Microbiologia, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal
- Corresponding author. Fax: +351 222 003 977.

Received 10 August 2009; received in revised form 9 October 2009; accepted 13 October 2009. published online 19 October 2009.

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-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.

Keywords: p53, Protein kinase C isoform, Cell growth, Cell cycle, p53 phosphorylation, Yeast

Abbreviations: CFU, colony-forming units, PI, propidium iodide, OD, optical density, PKC, protein kinase C, ROS, reactive oxygen species, WT, Wild-type