Prokaryotic toxin Kid inhibits proliferation of eukaryotic cells and triggers apoptosis in human cells, whilst its natural antidote Kis, protects from these effects. Modulation of the intracellular relative levels of Kid and Kis have been used to selectively regulate cell proliferation (or cell death) in eukaryotic cells. This approach may allow targeted cell ablation of cancer cells or of specific cell lineage during development and has potential in gene therapy strategies and in developmental studies. To achieve these goals it is important to understand Kid s mode of action in eukaryotic cells. Preliminary results show that Kid inhibits eukaryotic DNA replication, arrests yeast cells in G1 phase of the cell cycle and inhibits proliferation of human cells which die by apoptosis. On the basis of these observations, the main purpose of this project is to investigate the precise mechanism of action of Kid in human cells and how it is linked to inhibition of cell proliferation and to the activation of cell death.