Blau L, Knirsh R, Ben-Dror I, Oren S, Kuphal S, Hau P, Proescholdt M, Bosserhoff AK, Vardimon L (2012)
Publication Type: Journal article
Publication year: 2012
Book Volume: 109
Pages Range: E2875-E2884
Journal Issue: 42
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′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.
APA:
Blau, L., Knirsh, R., Ben-Dror, I., Oren, S., Kuphal, S., Hau, P.,... Vardimon, L. (2012). Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation. Proceedings of the National Academy of Sciences of the United States of America, 109(42), E2875-E2884. https://doi.org/10.1073/pnas.1203659109
MLA:
Blau, Lior, et al. "Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation." Proceedings of the National Academy of Sciences of the United States of America 109.42 (2012): E2875-E2884.
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