Ammodytoxin, a secretory phospholipase A₂, inhibits G₂ cell-cycle arrest in the yeast Saccharomyces cerevisiae Available to Purchase

Ammodytoxin (Atx), an sPLA₂ (secretory phospholipase A₂), binds to γ and ε isoforms of porcine 14-3-3 proteins in vitro. 14-3-3 proteins are evolutionarily conserved eukaryotic regulatory proteins involved in a variety of biological processes, including cell-cycle regulation. We have now shown that Atx binds to yeast 14-3-3 proteins with an affinity similar to that for the mammalian isoforms. Thus yeast Saccharomyces cerevisiae can be used as a model eukaryotic cell, which lacks endogenous phospholipases A₂, to assess the in vivo relevance of this interaction. Atx was expressed in yeast cells and shown to be biologically active inside the cells. It inhibited G₂ cell-cycle arrest in yeast, which is regulated by 14-3-3 proteins. Interference with the cell cycle indicates a possible mechanism by which sPLA₂s are able to cause the opposing effects, proliferation and apoptosis, in mammalian cells.