Differential regulation of p53 function by protein kinase C isoforms revealed by a yeast cell system.
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.
Laboratório de Microbiologia, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, 4050-047 Porto, Portugal.
Isabel
I
Coutinho
Gil
G
Pereira
Mariana
M
Leão
Jorge
J
Gonçalves
Manuela
M
Côrte-Real
Lucília
L
Saraiva
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002453:Cell Cycle; D002455:Cell Division; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014170:Transformation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000166:cytology / Q000235:genetics / Q000254:growth & development; D000099221:Protein Kinase C zeta
D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D016159:Tumor Suppressor Protein p53; D000099221:Protein Kinase C zeta