Abstract
E4orf6 is one of the oncogene products of adenovirus, and it also has an important role for transportation of cellular and viral messenger RNA (mRNA) during the late phase of virus infection. We previously revealed that E4orf6 controls the fate of AU-rich element (ARE) containing mRNA by perturbing the chromosome maintenance region 1-dependent export mechanism. Here, we show that E4orf6 stabilizes ARE–mRNA through the region required for its oncogenic activity and ubiquitin E3 ligase assembly. Cells that failed to stabilize ARE–mRNA after HuR knockdown were unable to produce colonies in soft agar, even when E4orf6 was expressed. Furthermore, the stabilized ARE–mRNA induced the transformation of rodent immortalized cells. These findings indicate that stabilized ARE–mRNA is necessary, if not all, for the oncogenic activity of E4orf6 and has the potential to transform cells, at least under a certain condition.
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Acknowledgements
We thank T Dobner for donating the E4orf6 mutant and mutant adenovirus expression plasmids, H Ariga for donating the c-myc expression vector, K Yoshida for donating the c-fos expression vector and L Agami for donating the pSUPER plasmid. This work was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and by a Grant-in Aid from the Akiyama Foundation.
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Kuroshima, T., Aoyagi, M., Yasuda, M. et al. Viral-mediated stabilization of AU-rich element containing mRNA contributes to cell transformation. Oncogene 30, 2912–2920 (2011). https://doi.org/10.1038/onc.2011.14
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DOI: https://doi.org/10.1038/onc.2011.14
