RRC ID 46366
著者 Huang CY, Chen JY, Wu SC, Tan CH, Tzeng RY, Lu PJ, Wu YF, Chen RH, Wu YC.
タイトル C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase.
ジャーナル PLoS One
Abstract Programmed cell death (apoptosis) is essential for the development and homeostasis of metazoans. The central step in the execution of programmed cell death is the activation of caspases. In C. elegans, the core cell death regulators EGL-1(a BH3 domain-containing protein), CED-9 (Bcl-2), and CED-4 (Apaf-1) act in an inhibitory cascade to activate the CED-3 caspase. Here we have identified an additional component eif-3.K (eukaryotic translation initiation factor 3 subunit k) that acts upstream of ced-3 to promote programmed cell death. The loss of eif-3.K reduced cell deaths in both somatic and germ cells, whereas the overexpression of eif-3.K resulted in a slight but significant increase in cell death. Using a cell-specific promoter, we show that eif-3.K promotes cell death in a cell-autonomous manner. In addition, the loss of eif-3.K significantly suppressed cell death-induced through the overexpression of ced-4, but not ced-3, indicating a distinct requirement for eif-3.K in apoptosis. Reciprocally, a loss of ced-3 suppressed cell death induced by the overexpression of eif-3.K. These results indicate that eif-3.K requires ced-3 to promote programmed cell death and that eif-3.K acts upstream of ced-3 to promote this process. The EIF-3.K protein is ubiquitously expressed in embryos and larvae and localizes to the cytoplasm. A structure-function analysis revealed that the 61 amino acid long WH domain of EIF-3.K, potentially involved in protein-DNA/RNA interactions, is both necessary and sufficient for the cell death-promoting activity of EIF-3.K. Because human eIF3k was able to partially substitute for C. elegans eif-3.K in the promotion of cell death, this WH domain-dependent EIF-3.K-mediated cell death process has potentially been conserved throughout evolution.
巻・号 7(5)
ページ e36584
公開日 2012-1-1
DOI 10.1371/journal.pone.0036584
PII PONE-D-12-00735
PMID 22590572
PMC PMC3348885
MeSH Animals Animals, Genetically Modified / embryology Animals, Genetically Modified / genetics Animals, Genetically Modified / metabolism Apoptosis / physiology* Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / biosynthesis* Caenorhabditis elegans Proteins / genetics Caspases / biosynthesis* Caspases / genetics Cell Death / physiology Cells, Cultured Eukaryotic Initiation Factor-3 Gene Expression Regulation, Enzymologic / physiology* Genetic Complementation Test Germ Cells / cytology Germ Cells / metabolism Humans Larva / cytology Larva / metabolism
IF 2.74
引用数 7
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm2486 tm2873 tm3077