Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells
Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells
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DOI：
10.1038/sj.onc.1209495
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发表时间：
2006-08-10
期刊：
影响因子：
8
通讯作者：
Nelson, M. A.
中科院分区：
文献类型：
--
作者：
Shi, J.;Kahle, A.;Nelson, M. A.
真核细胞起始因子3f(EIF3f)是多亚基eIF3复合体的p47亚基。EIF3在翻译启动过程中起着重要的作用。在本研究中，我们研究了eIF3f在肿瘤细胞翻译和凋亡中的生物学功能。我们首次使用癌症专家证明了eIF3f在大多数人类肿瘤中表达下调。LING阵列，并经实时定量逆转录聚合酶链式反应证实在黑色素瘤和胰腺癌中的表达。过表达eIF3f可抑制黑色素瘤和胰腺癌细胞的增殖并诱导其凋亡。沉默eIF3f可保护黑色素瘤细胞免于凋亡。我们进一步研究了eIF3f的生物学功能。体外翻译研究表明，eIF3f是翻译的负调控因子，其翻译调控功能需要eIF3f的170-248位氨基酸之间的区域。EIF3f的异位表达抑制翻译和细胞整体蛋白质合成。核糖体专家。LE和核糖体RNA(RRNA)片段化分析表明，eIF3f使核糖体减少，这可能与rRNA降解有关。我们认为eIF3f可能在细胞凋亡过程中的核糖体降解中起作用。这些数据为eIF3f的细胞功能以及翻译启动和细胞凋亡之间的联系提供了重要的见解。
The eukaryotic initiation factor 3f (eIF3f) is the p47 subunit of the multi-subunit eIF3 complex. eIF3 plays an important role in translation initiation. In the present study, we investigate the biological function of eIF3f in translation and apoptosis in tumor cells. We demonstrated for the first time that eIF3f is downregulated in most human tumors using a cancer pro. ling array and confirmed by real-time reverse transcription PCR in melanoma and pancreatic cancer. Overexpression of eIF3f inhibits cell proliferation and induces apoptosis in melanoma and pancreatic cancer cells. Silencing of eIF3f protects melanoma cells from apoptosis. We further investigated the biological function of eIF3f. In vitro translation studies indicate that eIF3f is a negative regulator of translation and that the region between amino acids 170 and 248 of eIF3f is required for its translation regulatory function. Ectopic expression of eIF3f inhibits translation and overall cellular protein synthesis. Ribosome pro. le and ribosomal RNA (rRNA) fragmentation assays revealed that eIF3f reduces ribosomes, which may be associated with rRNA degradation. We propose that eIF3f may play a role in ribosome degradation during apoptosis. These data provide critical insights into the cellular function of eIF3f and in linking translation initiation and apoptosis.