An eEF1A1 truncation encoded by PTI-1 exerts its oncogenic effect inside the nucleus.
An eEF1A1 truncation encoded by PTI-1 exerts its oncogenic effect inside the nucleus.
复制标题
DOI：
10.1186/1475-2867-14-17
复制
发表时间：
2014-02-26
影响因子：
5.8
通讯作者：
Knudsen CR
中科院分区：
文献类型：
--
作者：
Dahl LD;Corydon TJ;Ränkel L;Nielsen KM;Füchtbauer EM;Knudsen CR
癌基因 PTI-1 最初是通过其转化大鼠成纤维细胞的能力从前列腺癌细胞系中分离出来的。 PTI-1 mRNA具有非常古怪的结构，因为5'UTR类似于原核23S rRNA，而主要开放阅读框和3'UTR对应于编码人类翻译延伸因子eEF1A1的mRNA的一部分。因此，最大的开放阅读框编码了 eEF1A1 的截短版本，缺少前 67 个氨基酸，但具有三个独特的 N 端氨基酸。此前，UTR 被证明是 PTI-1 转录本转化能力的先决条件。在这项研究中，我们研究了 UTR 在调节蛋白质表达和定位中的可能作用。在体外和体内研究了许多 PTI-1 mRNA 变体的蛋白质表达谱。此外，通过监测表达这些 mRNA 的稳定转染细胞在裸鼠中诱导肿瘤并在细胞培养物中形成病灶的能力，确定了相同 PTI-1 mRNA 的致癌潜力。最后，通过荧光显微镜确定这些 mRNA 表达的 PTI-1 蛋白的细胞定位。研究发现 PTI-1 mRNA 会产生多种蛋白质产物，这些蛋白质产物可能源自主要开放阅读框内下游、框内 AUG 的翻译起始。至少一种截短的蛋白质变体也被发现具有致癌性。然而，UTR 似乎并不影响这些截短的蛋白质产品的数量和特性。相反，我们的定位研究表明转录本的 UTR 促进编码蛋白的核定位。 PTI-1 mRNA 的翻译会产生多种蛋白质产物，其中截短的变体可能在细胞转化过程中发挥主要作用。 PTI-1 UTR 似乎在翻译调节中没有发挥作用，但似乎有助于 PTI-1 蛋白的核定位。这表明 PTI-1 蛋白在细胞核内发挥其致癌功能。
The oncogene PTI-1 was originally isolated from a prostate cancer cell line by its capability to transform rat fibroblasts. The PTI-1 mRNA has a very eccentric structure as the 5′UTR is similar to prokaryotic 23S rRNA, while the major open reading frame and the 3′UTR corresponds to a part of the mRNA encoding human translation elongation factor eEF1A1. Thus, the largest open reading frame encodes a truncated version of eEF1A1 lacking the first 67 amino acids, while having three unique N-terminal amino acids. Previously, the UTRs were shown to be a prerequisite for the transforming capacity of the PTI-1 transcript. In this study, we have investigated the possible role of the UTRs in regulating protein expression and localization. The protein expression profiles of a number of PTI-1 mRNA variants were studied in vitro and in vivo. Furthermore, the oncogenic potentials of the same PTI-1 mRNAs were determined by monitoring the capacities of stably transfected cells expressing these mRNAs to induce tumors in nude mice and form foci in cell culture. Finally, the cellular localizations of PTI-1 proteins expressed from these mRNAs were determined by fluorescence microscopy. The PTI-1 mRNA was found to give rise to multiple protein products that potentially originate from translation initiation at downstream, inframe AUGs within the major open reading frame. At least one of the truncated protein variants was also found to be oncogenic. However, the UTRs did not appear to influence the amount and identities of these truncated protein products. In contrast, our localization studies showed that the UTRs of the transcript promote a nuclear localization of the encoded protein(s). Translation of the PTI-1 mRNA results in multiple protein products of which (a) truncated variant(s) may play a predominant role during cellular transformation. The PTI-1 UTRs did not seem to play a role in translation regulation, but appeared to contribute to a nuclear localization of the PTI-1 protein(s). This indicates that the PTI-1 protein(s) exert(s) its/their oncogenic function inside the nucleus.
登录
查看更多内容
DOI：
10.1083/jcb.115.4.887
发表时间：
1991-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kozak M
通讯作者：
Kozak M
DOI：
10.1111/j.1749-6632.2009.04909.x
发表时间：
2009-01-01
期刊：
NATURAL COMPOUNDS AND THEIR ROLE IN APOPTOTIC CELL SIGNALING PATHWAYS
影响因子：
--
作者：
Lee, Mee-Hyun;Surh, Young-Joon
通讯作者：
Surh, Young-Joon
DOI：
10.1152/ajprenal.00331.2009
发表时间：
2009-12-01
影响因子：
4.2
作者：
Faerch, Mia;Christensen, Jane H.;Corydon, Thomas J.
通讯作者：
Corydon, Thomas J.
影响因子：
4.8
作者：
Dalgleish, G;Veyrune, JL;Hesketh, J
通讯作者：
Hesketh, J
DOI：
10.1046/j.1432-1033.2003.03713.x
发表时间：
2003-08-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Dapas, B;Tell, G;Scaggiante, B
通讯作者：
Scaggiante, B