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

被引:20
作者
Coutinho, Isabel [1 ]
Pereira, Gil [1 ]
Leao, Mariana [1 ]
Goncalves, Jorge [2 ]
Corte-Real, Manuela [3 ]
Saraiva, Lucilia [1 ]
机构
[1] Univ Porto, Fac Farm, REQUIMTE, Microbiol Lab, P-4050047 Oporto, Portugal
[2] Univ Porto, Fac Farm, REQUIMTE, Farmacol Lab, P-4050047 Oporto, Portugal
[3] Univ Minho, Ctr Biol Mol & Ambiental, P-4710057 Braga, Portugal
关键词
p53; Protein kinase C isoform; Cell growth; Cell cycle; phosphorylation; Yeast; SACCHAROMYCES-CEREVISIAE; TUMOR-SUPPRESSOR; APOPTOSIS; PHOSPHORYLATION; ACTIVATION;
D O I
10.1016/j.febslet.2009.10.030
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:3582 / 3588
页数:7
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