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

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.
Mesh Terms:
Acetylation, Adult, Cell Adhesion Molecules, Cell Line, Tumor, Cell Proliferation, Chromatin, Disease Progression, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Neoplastic, Glioma, Human Umbilical Vein Endothelial Cells, Humans, Male, Models, Biological, Neoplasm Invasiveness, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-jun, Transcriptional Activation, p300-CBP Transcription Factors
Mol. Cell. Biol.
Date: Mar. 01, 2017
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