TY - JOUR
AU - Willis, A E
AB - 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.
TI - Upregulated c-myc expression in multiple myeloma by internal ribosome entry results from increased interactions with and expression of PTB-1 and YB-1
JF - Oncogene
DO - 10.1038/onc.2010.31
DA - 2010-05-13
UR - https://www.deepdyve.com/lp/springer-journals/upregulated-c-myc-expression-in-multiple-myeloma-by-internal-ribosome-B7eeAN5ZI4
SP - 2884
EP - 2891
VL - 29
IS - 19
DP - DeepDyve
ER -