程序性細(xì)胞死亡對后生動物的發(fā)育及體內(nèi)平衡至關(guān)重要,，該過程中最重要的一步是半胱天冬酶（caspase）的激活。在秀麗隱桿線蟲中,，細(xì)胞死亡核心調(diào)節(jié)因子EGL-1（是一種含有BH3結(jié)構(gòu)域的蛋白）,、CED-9 (Bcl-2)及CED-4 (Apaf-1)作用在一個抑制性級聯(lián)反應(yīng)來激活CED-3 caspase。
近日,，來自國立臺灣大學(xué)的研究人員發(fā)現(xiàn),，秀麗隱桿線蟲的EIF-3.K通過CED-3 caspase促進(jìn)了程序性細(xì)胞死亡。相關(guān)論文發(fā)表在5月9日的PLoS ONE,。
在該研究中,，他們鑒定了一個作用在ced-3上游來促進(jìn)程序性細(xì)胞死亡的額外組件eif-3.K（真核生物翻譯起始因子3亞基k）。
研究發(fā)現(xiàn),，在體細(xì)胞及生殖細(xì)胞,，失去eif-3.K后細(xì)胞死亡減少，然而eif-3.K的過表達(dá)則顯著增加了細(xì)胞死亡,。
使用一個細(xì)胞特異性的啟動子,，他們發(fā)現(xiàn)，eif-3.K促進(jìn)了細(xì)胞自發(fā)死亡,。除此以外,，在失去eif-3.K后，通過ced-4而不是ced-3的過表達(dá),，細(xì)胞死亡表現(xiàn)出顯著抑制,。這表明了在凋亡過程中對eif-3.K的不同需求。相反的,，ced-3的丟失則會通過eif-3.K的過表達(dá)來抑制細(xì)胞死亡,。
這些結(jié)果表明，eif-3.K需要ced-3來促進(jìn)程序性細(xì)胞死亡,，而且eif-3.K是作用在ced-3上游促進(jìn)了該過程,。
EIF-3.K蛋白廣泛表達(dá)于胚胎及幼蟲,，并定位于細(xì)胞質(zhì)。結(jié)構(gòu)-功能分析表明,，位于EIF-3.K上61個氨基酸的WH結(jié)構(gòu)域,，可能與蛋白質(zhì)和DNA/RNA的相互作用有關(guān)，這對EIF-3.K促進(jìn)細(xì)胞死亡的活性是必須的,。
研究發(fā)現(xiàn),，在促進(jìn)細(xì)胞死亡過程中，人類eIF3k能夠部分取代秀麗隱桿線蟲的eif-3.K,。這表明在進(jìn)化過程中,，依賴WH結(jié)構(gòu)域的EIF-3.K介導(dǎo)的細(xì)胞死亡進(jìn)程可能是保守的。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0036584
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C. elegans EIF-3.K Promotes Programmed Cell Death through CED-3 Caspase
Chun-Yi Huang, Jia-Yun Chen, Shu-Chun Wu, Chieh-Hsiang Tan, Ruei-Ying Tzeng, Pei-Ju Lu, Yu-Feng Wu, Ruey-Hwa Chen, Yi-Chun Wu.
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.
