MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor-1

• Published in: eLife Vol. 10
• Main Authors: Popay, Tessa M, Wang, Jing, Adams, Clare M, Howard, Gregory Caleb, Codreanu, Simona G, Sherrod, Stacy D, McLean, John A, Thomas, Lance R, Lorey, Shelly L, Machida, Yuichi J, Weissmiller, April M, Eischen, Christine M, Liu, Qi, Tansey, William P
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 08-01-2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Antibodies; Biosynthesis; Burkitt Lymphoma; Burkitt's lymphoma; Cancer; Cancer Biology; Care and treatment; Cell cycle; Female; Flow cytometry; Gene Expression; Genes; Genes, Mitochondrial; Genetic research; Host Cell Factor C1 - genetics; Host Cell Factor C1 - metabolism; Humans; Malignancy; Metabolism; Metabolites; Mice; Mice, Nude; Mitochondria; Mutation; MYC; Myc protein; Non-Hodgkin's lymphomas; Organelle Biogenesis; Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; ribosome biogenesis; Ribosomes - physiology; Transcription factors; Tumorigenesis; Tumors; mouse; cancer; cancer biology; human; MYC; ribosome biogenesis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.60191

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC-HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.