Specific modulation of apoptosis and Bcl-xL phosphorylation in yeast by distinct mammalian protein kinase C isoforms.
Mammalian protein kinase C (PKC) isoforms have been subject of particular attention because of their ability to modulate apoptotic proteins. However, the roles played by each PKC isoform in apoptosis are still unclear. Here, expression of individual mammalian PKC isoforms in Saccharomyces cerevisiae is used as a new approach to study the role of each isoform in apoptosis. The four isoforms tested, excepting PKC-delta, stimulate S. cerevisiae acetic-acid-induced apoptosis essentially through a mitochondrial ROS-dependent pathway. However, their co-expression with Bcl-xL reveals a PKC-isoform-dependent modulation of Bcl-xL anti-apoptotic activity. A yeast pathway homologue to the mammalian SAPK/JNK is responsible for acetic-acid-induced Bcl-xL phosphorylation that is differently modulated by PKC isoforms. The data obtained suggest conservation of an ancient mechanism of apoptosis regulation in yeast and mammals and offer new insights into mammalian apoptosis modulation by PKC isoforms.
Saraiva
Lucília
L
Laboratório de Microbiologia, Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto (CEQOFFUP), Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal.
Silva
Rui D
RD
Pereira
Gil
G
Gonçalves
Jorge
J
Côrte-Real
Manuela
M
D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
C494811:BCL2L1 protein, human; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D051020:bcl-X Protein; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D019342:Acetic Acid