Reference - Detail
| 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 |
| PII | PGENETICS-D-13-02798 |
| 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 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4094 |