Pax2/5/8 proteins promote cell survival in C-elegans

Programmed cell death, or apoptosis, plays an important role during normal development, and is disrupted in a range of disease states. Although the key molecular events that occur during apoptosis are well characterized, less is known about the regulatory inputs that influence whether a cell will live or die. Work in mouse and human cells has shown that Pax transcription factors can influence cell death and promote cell survival, but the mechanism for their activity is not clear. Here, we show that two Pax2/5/8-related genes (egl-38 and pax-2) influence both somatic and germline cell death in C. elegans. Using genetic and molecular experiments, we show that the Pax proteins act as transcriptional regulators of ced-9, the C. elegans bcl-2 gene. These results identify a mechanism for Pax2/5/8-mediated regulation of cell death, and underscore the importance of transcriptional regulation of core apoptotic pathway genes in influencing cell survival.