程序性细胞死亡对后生动物的发育及体内平衡至关重要，该过程中最重要的一步是半胱天冬酶（caspase）的激活。在秀丽隐杆线虫中，细胞死亡核心调节因子EGL-1（是一种含有BH3结构域的蛋白）、CED-9 (Bcl-2)及CED-4 (Apaf-1)作用在一个抑制性级联反应来激活CED-3 caspase。
近日，来自国立台湾大学的研究人员发现，秀丽隐杆线虫的EIF-3.K通过CED-3 caspase促进了程序性细胞死亡。相关论文发表在5月9日的PLoS ONE。
在该研究中，他们鉴定了一个作用在ced-3上游来促进程序性细胞死亡的额外组件eif-3.K（真核生物翻译起始因子3亚基k）。
研究发现，在体细胞及生殖细胞，失去eif-3.K后细胞死亡减少，然而eif-3.K的过表达则显著增加了细胞死亡。
使用一个细胞特异性的启动子，他们发现，eif-3.K促进了细胞自发死亡。除此以外，在失去eif-3.K后，通过ced-4而不是ced-3的过表达，细胞死亡表现出显著抑制。这表明了在凋亡过程中对eif-3.K的不同需求。相反的，ced-3的丢失则会通过eif-3.K的过表达来抑制细胞死亡。
这些结果表明，eif-3.K需要ced-3来促进程序性细胞死亡，而且eif-3.K是作用在ced-3上游促进了该过程。
EIF-3.K蛋白广泛表达于胚胎及幼虫，并定位于细胞质。结构-功能分析表明，位于EIF-3.K上61个氨基酸的WH结构域，可能与蛋白质和DNA/RNA的相互作用有关，这对EIF-3.K促进细胞死亡的活性是必须的。
研究发现，在促进细胞死亡过程中，人类eIF3k能够部分取代秀丽隐杆线虫的eif-3.K。这表明在进化过程中，依赖WH结构域的EIF-3.K介导的细胞死亡进程可能是保守的。（生物谷Deepblue编译）
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.
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