Ammodytoxin, a secretory phospholipase A2, inhibits G2 cell-cycle arrest in the yeast Saccharomyces cerevisiae.
Ammodytoxin (Atx), an sPLA2 (secretory phospholipase A2), binds to g and e 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.
Petrovic
Uros
U
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, SI-1000 Ljubljana, Slovenia.
Sribar
Jernej
J
Matis
Maja
M
Anderluh
Gregor
G
Peter-Katalinić
Jasna
J
Krizaj
Igor
I
Gubensek
Franc
F
D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D016195:G2 Phase / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal; D006861:Hydrogen Peroxide; D009154:Mutation; D010741:Phospholipases A / Q000737:chemistry / Q000378:metabolism*; D054467:Phospholipases A2; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D048948:14-3-3 Proteins; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2