Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2

THE ces (for cell-death specification) genes of the nematode Caenorhabditis elegans the cell-death fate of individual cell types and are candidates for being the regulators of an evolutionarily conserved general pathway of programmed cell death(1-4). Here we present what we believe is the first molecular characterization of a ces gene. We cloned the gene ces-2, which is required to activate programmed cell death in the sister cells of the serotoninergic neurosecretory motor (NSM) neurons, and found that ces-2 encodes a basic region leucine-zipper (bZIP) transcription factor. The CES-2 protein is most similar to members of the PAR (proline- and acid-rich) subfamily of bZIP proteins and has DNA-binding specificity like that of PAR-family proteins. An oncogenic form of the mammalian PAR-family protein, hepatic leukaemia factor (HLF), is reported to effect programmed cell death in mammalian cells(5). On the basis of these observations, we suggest that some CES-2/PAR family transcription factors are evolutionarily conserved regulators of programmed cell death.