期刊
ONCOGENE
卷 29, 期 19, 页码 2884-2891出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.31
关键词
translation; IRES; c-myc; protein synthesis
资金
- BBSRC
- CRUK
- Biotechnology and Biological Sciences Research Council [BB/F006926/1] Funding Source: researchfish
- Medical Research Council [MC_UP_A600_1023] Funding Source: researchfish
- BBSRC [BB/F006926/1] Funding Source: UKRI
- MRC [MC_UP_A600_1023] Funding Source: UKRI
The 5' untranslated region of the proto-oncogene c-myc contains an internal ribosome entry segment (IRES) and c-myc translation can therefore be initiated by internal ribosome entry as well as by cap-dependent mechanisms. It has been shown previously that in patients with multiple myeloma (MM) and in MM-derived cell lines there is a C to T mutation in the c-myc IRES that increases IRES activity and the corresponding synthesis of c-myc protein although it is not fully understood how this occurs. Our data show that two recently identified c-myc IRES transacting factors, Y-box binding protein 1 (YB-1) and polypyrimidine tract-binding protein 1 (PTB-1), bind more strongly (approximately 3.5- and 2-fold respectively) to the mutated version of the c-myc IRES and in vitro these proteins exert their effect synergistically to stimulate IRES activity of the mutant IRES 4.5-fold more than the wild-type version. Importantly, we show that there is a strong correlation between the expression of PTB-1, YB-1 and c-myc in MM-derived cell lines, suggesting that by reducing either PTB-1 or YB-1 protein levels it is possible to decrease c-myc expression and inhibit cell proliferation of MM-derived cell lines. Oncogene (2010) 29, 2884-2891; doi: 10.1038/onc.2010.31; published online 1 March 2010
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