Regulation of BAG-1 IRES-mediated translation following chemotoxic stress

被引:55
作者
Dobbyn, H. C. [1 ]
Hill, K. [1 ]
Hamilton, T. L. [1 ]
Spriggs, K. A. [1 ]
Pickering, B. M. [1 ]
Coldwell, M. J. [1 ]
de Moor, C. H. [1 ]
Bushell, M. [1 ]
Willis, A. E. [1 ]
机构
[1] Univ Nottingham, Sch Pharm, Chair Canc Cell Biol, Nottingham NG7 2RD, England
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
BAG-1; translation; IRES; internal ribosome entry; polypyrimidine tract binding protein;
D O I
10.1038/sj.onc.1210723
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 tumorigenesis and chemoresistance. 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 ( PCBP1) 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, while 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 relocalization of PTB and PCBP1 from the nucleus to the cytoplasm.
引用
收藏
页码:1167 / 1174
页数:8
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