Novel cell death by downregulation of eEF1A1 expression in tetraploids
Novel cell death by downregulation of eEF1A1 expression in tetraploids
复制标题
DOI：
10.1038/cdd.2008.136
复制
发表时间：
2009-01-01
影响因子：
12.4
通讯作者：
Yonehara, S.
中科院分区：
文献类型：
--
作者：
Kobayashi, Y.;Yonehara, S.
当复制的姐妹染色单体在有丝分裂中没有正确压缩时，染色体就会错误分离，导致遗传不稳定的四倍体，这是已知的促进非整倍体恶性肿瘤的因素。在这里，我们表明，由受损的染色体凝聚产生的四倍体细胞可以通过一种不同于caspase依赖的细胞凋亡的新型细胞死亡来消除。细胞死亡与真核细胞翻译延长因子-1α1(eEF1A1/EF-1α)的表达下调以及其mRNA在加工小体(P小体)中的积聚有关。重要的是，外源eEF1A1的表达抑制了caspase非依赖性的细胞死亡，在诱导eEF1A1特异的短发夹状RNA的表达后，观察到了类似的细胞死亡。此外，在启动外源eEF1a表达后的1-2周培养中，自发产生的双核细胞的数量增加了数倍。综上所述，这种新的细胞死亡机制应该有助于消除异常的四倍体细胞，抑制肿瘤的形成。
When duplicated sister chromatids are not properly compacted in mitosis, chromosomes are mis-segregated, inducing genetically unstable tetraploidy known to facilitate aneuploid malignancies. Here, we show that tetraploid cells produced by impaired chromosomal condensation are eliminated by a novel type of cell death different from caspase-dependent apoptosis. The cell death was associated with downregulation of eukaryotic translation elongation factor-1 alpha 1 (eEF1A1/EF-1 alpha) expression in conjunction with accumulation of its mRNA in processing bodies ( P bodies). Importantly, expression of exogenous eEF1A1 was shown to inhibit the caspase-independent cell death, and a similar cell death was observed after inducing the expression of short hairpin RNA specific for eEF1A1. Furthermore, the number of spontaneously arising binucleated cells was indicated to increase several fold during 1- to 2-week cultivation after initiation of exogenous eEF1A expression. Taken together, the novel cell death machinery should help to eliminate abnormal tetraploid cells and inhibit tumorigenesis.