Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation

作者：Blau Lior; Knirsh Revital; Ben Dror Iris; Oren Sivan; Kuphal Silke; Hau Peter; Proescholdt Martin; Bosserhoff Anja Katrin; Vardimon Lily^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(42): E2875-E2884.

DOI：10.1073/pnas.1203659109

Although the protooncogene c-Jun plays a critical role in cell proliferation, cell death, and malignant transformation, DNA microarray screens have identified only a few human cancer types with aberrant expression of c-Jun. Here, we showthat c-Jun accumulation is robustly elevated in human glioblastoma and that this increase contributes to the malignant properties of the cells. Most importantly, the increase in c-Jun protein accumulation occurs with no corresponding increase in c-Jun mRNA or the half-life of the c-Jun protein but, rather, in the translatability of the transcript. The c-Jun 5%26apos; UTR harbors a potent internal ribosomal entry site (IRES) with a virus-like IRES domain that directs cap-independent translation in glioblastoma cells. Accumulation of c-Jun is not dependent on MAPK activity but can be stimulated by a cytoskeleton-dependent pathway. Our findings provide evidence that human c-Jun is an IRES-containing cellular transcript that contributes to cancer development through translational activation. This previously undescribed mechanism of c-Jun regulation might also be relevant to other types of human cancer and offers unique potential targets for therapy.

• 出版日期2012-10-16