title: 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 angiogenesisin vitroandin vivoConsistently, 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.
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Immunobiology, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China.
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China lijun37@mail.sysu.edu.cn limf@mail.sysu.edu.cn.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China lijun37@mail.sysu.edu.cn limf@mail.sysu.edu.cn.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D000107:Acetylation; D000328:Adult; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D018450:Disease Progression; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015533:Transcriptional Activation / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D015815:Cell Adhesion Molecules; D002843:Chromatin; D008565:Membrane Proteins; D016755:Proto-Oncogene Proteins c-jun; D016601:RNA-Binding Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C483039:MTDH protein, human
keywords: E1A binding protein p300 (p300); acetylation; astrocyte elevated gene 1 (AEG-1); c-Jun transcription factor; glioma