Blau, Lior and Knirsh, Revital and Ben-Dror, Iris and Oren, Sivan and Kuphal, Silke and Hau, Peter and Proescholdt, Martin and Bosserhoff, Anja-Katrin and Vardimon, Lily (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. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSCRIPTION FACTOR; GLUCOCORTICOID-RECEPTOR; PROTEIN-KINASES; HIGH-GRADE; E-CADHERIN; AP-1; GLIOMA; CYTOSKELETAL; INVASION; PROLIFERATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Neurologie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 May 2020 05:51 |
| Last Modified: | 05 May 2020 05:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17943 |
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