Regulation of BAG-1 IRES-mediated translation following chemotoxic stress.
Regulation of BAG-1 IRES-mediated translation following chemotoxic stress.
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在趋化应激后，BAG-1 IRES介导的翻译调节。
DOI：
10.1038/sj.onc.1210723
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发表时间：
2008-02-14
期刊：
影响因子：
8
通讯作者：
Willis, A. E.
中科院分区：
文献类型：
--
作者：
Dobbyn, H. C.;Hill, K.;Hamilton, T. L.;Spriggs, K. A.;Pickering, B. M.;Coldwell, M. J.;de Moor, C. H.;Bushell, M.;Willis, A. E.
在哺乳动物细胞中，BAG-1有三种主要的亚型，分别为BAG-1L （p50）、BAG-1M （p46）和BAG-1S (p36)，它们作为促生存蛋白发挥作用，并与肿瘤发生和化疗耐药相关。BAG-1蛋白合成的起始可以通过帽依赖和帽不依赖两种机制发生，研究表明，BAG-1S的合成依赖于BAG-1 mRNA 5 ' UTR内核糖体进入段（IRES）的存在。我们已经证明BAG-1 IRES介导的翻译起始需要两个反式因子poly (rC) binding protein 1和polypyy嘧啶tract binding protein （PTB）才能起作用。前一种蛋白质允许BAG-1-IRES-RNA获得允许结合核糖体的结构，而后一种蛋白质似乎参与核糖体的招募。本研究表明，在细胞暴露于化学毒性药物长春新碱（而非顺铂）后，BAG-1 IRES维持BAG-1蛋白的合成，这在一定程度上是由于PTB和PCBP1从细胞核重新定位到细胞质。
There are three major isoforms of BAG-1 in mammalian cells, termed BAG-1L (p50), BAG-1M (p46) and BAG-1S (p36) that function as pro-survival proteins and are associated with tumourigenesis and chemo-resistance. Initiation of BAG-1 protein synthesis can occur by both cap-dependent and cap-independent mechanisms and it has been shown that synthesis of BAG-1S is dependent upon the presence of an internal ribosome entry segment (IRES) in the 5′ UTR of BAG-1 mRNA. We have shown previously that BAG-1 IRES meditated-initiation of translation requires two trans-acting factors poly (rC) binding protein 1 and polypyrimidine tract binding protein (PTB) for function. The former protein allows BAG-1-IRES-RNA to attain a structure that permits binding of the ribosome whilst the latter protein appears to be involved in ribosome recruitment. Here we show that the BAG-1 IRES maintains synthesis of BAG-1 protein following exposure of cells to the chemotoxic drug vincristine but not to cisplatin and that this is brought about, in part, by the re-localisation of PTB and PCBP1 from the nucleus to the cytoplasm.
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