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

eLife | 2021

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.

Pubmed ID: 33416496 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA200709
  • Agency: NCI NIH HHS, United States
    Id: T32 CA119925
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK058404
  • Agency: NEI NIH HHS, United States
    Id: P30 EY008126
  • Agency: NCI NIH HHS, United States
    Id: P30 CA056036
  • Agency: NCI NIH HHS, United States
    Id: R50 CA211305
  • Agency: NCI NIH HHS, United States
    Id: P30 CA068485
  • Agency: NCI NIH HHS, United States
    Id: R01 CA148950

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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