Death associated proteins (DAPs): from gene identification to the analysis of their apoptotic and tumor suppressive functions

The process of apoptosis (programmed cell death) has become the subject of intensive and extensive research over the past few years. Various approaches are being used to identify and study genes which function as positive mediators of apoptosis. Here, we address a novel approach of gene cloning aimed at isolating intracellular death promoting genes by utilizing a functional screen. This method, called TKO, was based on transfection of cells with an anti-sense cDNA library, followed by the selection of transfectants which survived in the contin-uous presence of a killing cytokine – interferon-g. It led to the identification of five novel apoptotic genes and to the finding that a known protease – cathepsin D, is actively recruited to the death process. The five novel apoptotic genes (named DAP genes for: Death Asso