Fig. 7: The toxicity of SETD8 inhibitors correlates with ribosome biogenesis.
From: SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis
A sgRNA enrichment scores from a CRISPR resistance screen for C23 (10 μM) in KBM7 cells, 10 days after starting the treatment. Bubble plots illustrate the median enrichment of all sgRNAs targeting a given gene over DMSO, bubble sizes indicate significance. Significantly enriched sgRNAs (blue bubbles) were used for the enrichment analysis shown in B. B Gene Ontology “Biological process” pathways that are significantly enriched among the list of significantly enriched sgRNAs selected from A. Note that most pathways are related to RNA metabolism and ribosome biogenesis. C Effect of increasing doses of C23 on the viability of Ba/F3MYCER cells, in the presence or absence of 4-OHT to promote the nuclear translocation of MYCER. D Effect of increasing doses of C23 on the viability of U2OS cells, previously transfected with siRNAs targeting MYC or a control siRNA. E Effect of increasing doses of C23 on the viability of Tsc2+/+ and Tsc2−/− MEF. Note that both cell lines were also p53 deficient, which is necessary to enable the growth of Tsc2−/− MEF. ***P < 0.001; ANOVA.
