Open AccessTranscriptional Activation of MYC-Induced Genes by GCN5 Promotes B-cell Lymphomagenesis
Author(s) -
Aimee T. Farria,
Joshua B. Plummer,
Andrew P. Salinger,
Jianjun Shen,
Kevin Lin,
Yao Lu,
Kevin M. McBride,
Evangelia Koutelou,
Sharon Y.R. Dent
Publication year - 2020
Publication title -
cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.103
H-Index - 449
eISSN - 1538-7445
pISSN - 0008-5472
DOI - 10.1158/0008-5472.can-20-2379
Subject(s) - carcinogenesis , cancer research , coactivator , biology , proto oncogene proteins c myc , cell cycle , cell cycle progression , gene , chromatin , cancer , lymphoma , cell , cell growth , microbiology and biotechnology , gene expression , transcription factor , genetics , immunology
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.