Astrocyte Elevated Gene 1 Interacts with Acetyltransferase p300 and c-Jun To Promote Tumor Aggressiveness

ABSTRACT

Astrocyte elevated gene 1 (AEG-1) is an oncoprotein that strongly promotes the development and progression of cancers. However, the detailed underlying mechanisms through which AEG-1 enhances tumor development and progression remain to be determined. In this study, we identified c-Jun and p300 to be novel interacting partners of AEG-1 in gliomas. AEG-1 promoted c-Jun transcriptional activity by interacting with the c-Jun/p300 complex and inducing c-Jun acetylation. Furthermore, the AEG-1/c-Jun/p300 complex was found to bind the promoter of c-Jun downstream targeted genes, consequently establishing an acetylated chromatin state that favors transcriptional activation. Importantly, AEG-1/p300-mediated c-Jun acetylation resulted in the development of a more aggressive malignant phenotype in gliomas through a drastic increase in glioma cell proliferation and angiogenesis in vitro and in vivo. Consistently, the AEG-1 expression levels in clinical glioma specimens correlated with the status of c-Jun activation. Taken together, our results suggest that AEG-1 mediates a novel epigenetic mechanism that enhances c-Jun transcriptional activity to induce glioma progression and that AEG-1 might be a novel, potential target for the treatment of gliomas.

KEYWORDS:

• E1A binding protein p300 (p300)
• acetylation
• astrocyte elevated gene 1 (AEG-1)
• c-Jun transcription factor
• glioma

Supplemental material for this article may be found at https://doi.org/10.1128/MCB.00456-16.

ACKNOWLEDGMENTS

This work was supported by the Natural Science Foundation of China (no. 81272339, 81330058, 91529301, and 81325013), Guangdong Natural Science Funds for Distinguished Young Scholars (2014A030306023), the Science and Technology of Guangdong Province (no. 2014A030313008), and the National Science and Technique Major Project (201305017).

We declare no competing financial interests.