dc.contributor.author | Hirose, Takashi | |
dc.contributor.author | Horvitz, Howard Robert | |
dc.date.accessioned | 2014-10-20T12:16:15Z | |
dc.date.available | 2014-10-20T12:16:15Z | |
dc.date.issued | 2014-08 | |
dc.date.submitted | 2013-10 | |
dc.identifier.issn | 1553-7404 | |
dc.identifier.issn | 1553-7390 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/90973 | |
dc.description.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. | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute | en_US |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pgen.1004512 | en_US |
dc.rights | Creative Commons Attribution | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | Public Library of Science | en_US |
dc.title | The Translational Regulators GCN-1 and ABCF-3 Act Together to Promote Apoptosis in C. elegans | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Hirose, Takashi, and H. Robert Horvitz. “The Translational Regulators GCN-1 and ABCF-3 Act Together to Promote Apoptosis in C. Elegans.” Edited by Andrew D. Chisholm. PLoS Genet 10, no. 8 (August 7, 2014): e1004512. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.mitauthor | Hirose, Takashi | en_US |
dc.contributor.mitauthor | Horvitz, H. Robert | en_US |
dc.relation.journal | PLoS Genetics | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Hirose, Takashi; Horvitz, H. Robert | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9964-9613 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |