Transcriptional Activation of MYC-Induced Genes by GCN5 Promotes B-cell Lymphomagenesis
| Autor: | Yue Lu, Kevin M. McBride, Andrew P. Salinger, Evangelia Koutelou, Aimee T. Farria, Jianjun Shen, Joshua B. Plummer, Sharon Y.R. Dent, Kevin Lin |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Transcriptional Activation 0301 basic medicine Cancer Research Lymphoma B-Cell Genotype Carcinogenesis Mice Transgenic Biology medicine.disease_cause Article Proto-Oncogene Proteins c-myc Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression Coactivator medicine Animals p300-CBP Transcription Factors Gene Cells Cultured B cell B-Lymphocytes Cancer Cell cycle medicine.disease Mice Inbred C57BL enzymes and coenzymes (carbohydrates) 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis Cancer research Female Gene Deletion DNA |
| Zdroj: | Cancer Res |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes, including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here, we show that GCN5 is an essential coactivator of cell-cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Eμ-Myc mouse model of B-cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of Myc. Significance: Our results provide important proof of principle for Gcn5 functions in formation and progression of Myc-driven cancers, suggesting that GCN5 may be a viable target for development of new cancer therapies. |
| Databáze: | OpenAIRE |
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