Upregulated c-myc expression in multiple myeloma by internal ribosome entry results from increased interactions with and expression of PTB-1 and YB-1
- 1 March 2010
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 29 (19), 2884-2891
- https://doi.org/10.1038/onc.2010.31
Abstract
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 trans-acting 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.Keywords
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