Fig. 1.

Schematic of the roles of key cellular gene dependencies in PEL cell lines. (A) PEL cell lines depend on the PSODs IRF4 and BATF to drive super-enhancer-mediated expression of common essential MYC, and PSODs IRF4 and CCND2. vIRF3 is involved at least in the regulation of the IRF4-SE. SE-mediated gene expression can be disrupted using BET inhibitors (BETi), while IRF4 can potentially be targeted using CMs (see also Fig 2C). (B) CCND2 dependency most likely involves CDK6 and can be targeted using cyclin-dependent kinase inhibitors. (C) PEL cell lines depend on the PSOD CFLAR, potentially downstream of death receptor signaling, and the skewed pan-essential gene MCL1, which prevents apoptosis via the mitochondrial pathway. MCL1 can be targeted using specific inhibitors. (D) PEL cell lines depend on the p53 inhibitor MDM2. LANA is known to participate in a complex with MDM2 and p53 and contribute to p53 inhibition. The interaction between p53 and MDM2 can be disrupted using Nutlins. Proteins encoded by selectively essential genes are in blue, those encoded by pan-essential genes are in green and essential viral proteins are in orange. Ub: ubiquitin.