An apoptosis-inducing isoform of Neu differentiation factor (NDF) identified using a novel screen for dominant, apoptosis-inducing genes

Apoptosis is a genetically programmed series of events that results in cell death. As a consequence, it is difficult to identify dominant genes that play a role in this process using genetic selections in conventional cell culture systems. Accordingly, we have established an efficient expression screen to isolate dominant, apoptosis-inducing genes. The assay is based on the apoptotic morphology induced in the human kidney cell line 293 after transient transfection of small plasmid pools from normalized cDNA expression libraries. Using this assay, we isolated a novel isoform of the proto-oncogene Neu differentiation factor (NDF), a ligand for erbB receptor tyrosine kinases. Several lines of experimental evidence indicate that this gene kills in a cell-autonomous fashion and independently of known erbB receptors. This apoptotic property of an NDF isoform is readily contrasted with NDF's transforming potential and might balance the tendency to tumorigenesis in cells that overexpress NDF.