RRC ID 45745
Author Hirose T, Horvitz HR.
Title The translational regulators GCN-1 and ABCF-3 act together to promote apoptosis in C. elegans.
Journal PLoS Genet
Abstract 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.
Volume 10(8)
Pages e1004512
Published 2014-8-1
DOI 10.1371/journal.pgen.1004512
PMID 25101958
PMC PMC4125083
MeSH ATP-Binding Cassette Transporters / genetics* Animals Apoptosis / genetics* Caenorhabditis elegans Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics* Carrier Proteins / biosynthesis Carrier Proteins / genetics* Eukaryotic Initiation Factor-2 / biosynthesis Eukaryotic Initiation Factor-2 / genetics Gene Expression Regulation, Developmental / radiation effects Germ Cells / radiation effects Protein Biosynthesis* RNA, Messenger / biosynthesis Radiation, Ionizing
IF 5.175
Times Cited 13
C.elegans tm4094