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

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

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 109

Pages Range: E2875-E2884

Journal Issue: 42

DOI: 10.1073/pnas.1203659109

Abstract

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.

Involved external institutions

Tel Aviv University IL Israel (IL) Universität Regensburg DE Germany (DE)

How to cite

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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