A non-death role of the yeast metacaspase: Yca1p alters cell cycle dynamics

• Published in: PloS one Vol. 3; no. 8; p. e2956
• Main Authors: Lee, Robin E C, Puente, Lawrence G, Kaern, Mads, Megeney, Lynn A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-08-2008; Public Library of Science (PLoS)
• Subjects: Amino Acid Substitution; Apoptosis; Baking yeast; Caspase; Caspases - genetics; Caspases - metabolism; Catalysis; Cell Biology; Cell Biology/Cellular Death and Stress Responses; Cell cycle; Cell Cycle - drug effects; Cell Cycle - genetics; Cell Cycle - physiology; Cell death; Cysteine - metabolism; Deactivation; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; DNA, Fungal - genetics; DNA, Fungal - metabolism; Eukaryotes; Fermentation; G1 Phase; Gene Expression Regulation, Fungal; Genes; Genomes; Growth factors; Hypotheses; Inactivation; Medical research; Medicine; Molecular Biology/Molecular Evolution; Mortality; Nocodazole; Nocodazole - pharmacology; Oxidative stress; Phenotype; Plasmids; Polyploidy; Promoter Regions, Genetic; Proteases; Proteasomes; Proteins; Proteolysis; Reactive oxygen species; S Phase; Saccharomyces cerevisiae; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Stem cells; Yeast; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002956

Caspase proteases are a conserved protein family predominantly known for engaging and executing apoptotic cell death. Nevertheless, in higher eukaryotes, caspases also influence a variety of cell behaviors including differentiation, proliferation and growth control. S. cerevisiae expresses a primordial caspase, yca1, and exhibits apoptosis-like death under certain stresses; however, the benefit of a dedicated death program to single cell organisms is controversial. In the absence of a clear rationale to justify the evolutionary retention of a death only pathway, we hypothesize that yca1 also influences non-apoptotic events. We report that genetic ablation and/or catalytic inactivation of Yca1p leads to a longer G1/S transition accompanied by slower growth in fermentation conditions. Downregulation of Yca1p proteolytic activity also results in failure to arrest during nocodazole treatment, indicating that Yca1p participates in the G2/M mitotic checkpoint. 20s proteasome activity and ROS staining of the Delta yca1 strain is indistinguishable from its isogenic control suggesting that putative regulation of the oxidative stress response by Yca1p does not instigate the cell cycle phenotype. Our results demonstrate multiple non-death roles for yca1 in the cell cycle.