BioProject

MYC is an oncoprotein transcription factor that is overexpressed in the majority cancers. More...

MYC is an oncoprotein transcription factor that is overexpressed in the majority cancers. Although MYC itself is considered undruggable, it may be possible to inhibit MYC by targeting the co-factors it uses to drive oncogenic gene expression patterns. Here, we use loss- and gain- of function approaches to interrogate how one MYC co-factor—Host Cell Factor (HCF)-1—contributes to MYC activity in a Burkitt lymphoma setting. We identify high-confidence direct targets of the MYC–HCF-1 interaction that are regulated through a recruitment-independent mechanism, including genes that control mitochondrial function and rate-limiting steps for ribosome biogenesis and translation. We describe how these gene expression events impact cell growth and metabolism, and demonstrate that the MYC–HCF-1 interaction is essential for tumor maintenance in vivo. This work highlights the MYC–HCF-1 interaction as a focal point for development of novel anti-cancer therapies. Overall design: The Burkitt lymphoma line Ramos cells was modified using CRISPR/Cas9-triggered homologous recombination to create either MYC switchable allele (MYC-WT, MYC-4A, MYC-VP16 HBM) or FKBP12FV N-terminally tagged HCF-1 cell lines. These cells were used for RNA-seq and ChIP-seq. Less...