Specific modulation of apoptosis and Bcl-xL phosphorylation in yeast by distinct mammalian protein kinase C isoforms

Lucília Saraiva1, Rui D Silva, Gil Pereira

  • 1Laboratório 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.

Insights

Mammalian protein kinase C (PKC) isoforms regulate apoptosis via mitochondrial reactive oxygen species (ROS). Yeast studies reveal conserved mechanisms, showing PKC isoforms modulate Bcl-xL activity and phosphorylation, offering insights into mammalian apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mammalian protein kinase C (PKC) isoforms are implicated in regulating apoptosis.
  • The specific roles of individual PKC isoforms in apoptosis remain incompletely understood.
  • Understanding these roles is crucial for insights into cell death pathways.

Purpose of the Study:

  • To investigate the function of individual mammalian protein kinase C (PKC) isoforms in apoptosis.
  • To explore the conserved mechanisms of apoptosis regulation between yeast and mammals.
  • To elucidate the modulation of anti-apoptotic protein Bcl-xL by PKC isoforms.

Main Methods:

  • Expression of individual mammalian PKC isoforms in Saccharomyces cerevisiae.
  • Induction of apoptosis using acetic acid in yeast models.
  • Analysis of mitochondrial reactive oxygen species (ROS) production.
  • Co-expression studies with Bcl-xL and assessment of Bcl-xL phosphorylation.

Main Results:

  • Most tested PKC isoforms, except PKC-delta, promote yeast apoptosis via mitochondrial ROS.
  • PKC isoforms differentially modulate the anti-apoptotic activity of Bcl-xL.
  • Yeast SAPK/JNK pathway homologue mediates acetic-acid-induced Bcl-xL phosphorylation, influenced by PKC isoforms.

Conclusions:

  • A conserved ancient mechanism for apoptosis regulation exists in yeast and mammals.
  • PKC isoforms play distinct roles in modulating apoptosis and Bcl-xL activity.
  • This study provides novel insights into mammalian apoptosis regulation by PKC isoforms using a yeast model.

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