The Translational Regulators GCN-1 and ABCF-3 Act Together to Promote Apoptosis in C. elegans

The proper regulation of apoptosis requires precise spatial and temporal control of gene expression. while the transcriptional and translational activation of pro-apoptotic genes is known to be crucial to triggering apoptosis,how different mechanisms cooperate to drive apoptosis is largely unexplored. here we report that pro-apoptotic transcriptional and translational regulators act in distinct pathways to promote programmed cell death. we show that the evolutionarily conserved c. elegans translational regulators gcn-1 and abcf-3 contribute to promoting the deaths of most somatic cells during development. gcn-1 and abcf-3 are not obviously involved in the physiological germ-cell deaths that occur during oocyte maturation. by striking contrast,these proteins play an essential role in the deaths of germ cells in response to ionizing irradiation. gcn-1 and abcf-3 are similarly co-expressed in many somatic and germ cells and physically interact in vivo,suggesting that gcn-1 and abcf-3 function as members of a protein complex. gcn-1 and abcf-3 are required for the basal level of phosphorylation of eukaryotic initiation factor 2α (eif2α),an evolutionarily conserved regulator of mrna translation. the s. cerevisiae homologs of gcn-1 and abcf-3,which are known to control eif2α phosphorylation,can substitute for the worm proteins in promoting somatic cell deaths in c. elegans. we conclude that gcn-1 and abcf-3 likely control translational initiation in c. elegans. gcn-1 and abcf-3 act independently of the anti-apoptotic bcl-2 homolog ced-9 and of transcriptional regulators that upregulate the pro-apoptotic bh3-only gene egl-1. our results suggest that gcn-1 and abcf-3 function in a pathway distinct from the canonical ced-9-regulated cell-death execution pathway. we propose that the translational regulators gcn-1 and abcf-3 maternally contribute to general apoptosis in c. elegans via a novel pathway and that the function of gcn-1 and abcf-3 in apoptosis might be evolutionarily conserved. © 2014 hirose,horvitz.