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

Abstract

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.

• Authors: Tessa M Popay, Jing Wang, Clare M Adams, Gregory Caleb Howard, Simona G Codreanu, Stacy D Sherrod, John A McLean, Lance R Thomas, Shelly L Lorey, Yuichi J Machida, April M Weissmiller, Christine M Eischen, Qi Liu, William P Tansey
• Journal: eLife (Elife) Vol. 10 (01 08 2021) ISSN: 2050-084X [Electronic] England
• PMID: 33416496 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021, Popay et al.

Chemical References

• Hcfc1 protein, mouse
• Host Cell Factor C1
• Myc protein, mouse
• Proto-Oncogene Proteins c-myc

Topics

• Animals
• Burkitt Lymphoma
• Female
• Gene Expression
• Genes, Mitochondrial
• Host Cell Factor C1 (genetics, metabolism)
• Humans
• Mice
• Mice, Nude
• Organelle Biogenesis
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Ribosomes (physiology)