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bioRxiv · 10.1101/2020.06.22.164764

MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1

Popay, T. M.·Wang, J.·Adams, C. M.·Codreanu, S. G.·Sherrod, S. D.·McLean, J. A.·Thomas, L. R.·Lorey, S. L.·Machida, Y. J.·Weissmiller, A. M.·Eischen, C. M.·Liu, Q.·Tansey, W.
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Abstract

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly-validated but challenging target for development of anti-cancer 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 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.

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Popay, T. M., Wang, J., Adams, C. M., Codreanu, S. G., Sherrod, S. D., McLean, J. A., Thomas, L. R., Lorey, S. L., Machida, Y. J., Weissmiller, A. M., Eischen, C. M., Liu, Q., Tansey, W.. 2020-06-23. MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1. https://doi.org/10.1101/2020.06.22.164764

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