Fig. 3.

Inactivation of DPH5 induces NF-κB and death receptor pathways. RNAseq data were obtained for untreated MCF7, TNF treated MCF7, and DPH5 inactivated MCF7 (SI Text S5). Genes that are significantly changed in their expression levels (MCF7 vs. TNF-MCF7, MCF7 vs. DPH5ko) were subjected to ingenuity upstream pathway analyses. Interestingly, differentially regulated pathways and regulators in both conditions overlap largely and share a common core of TNF- and IFNG-regulated genes, leading to a preactivation of death receptor signaling regulators as consequence of DPH5 deficiency and loss of diphthamide (orange: consequence of TNF treatment as well as DPH5ko; green: TNF treatment only; blue: DPH5ko only). Arrows indicate direct activating/inhibiting interactions between two nodes (based on literature findings) and dashed arrows indicate indirect interactions. Different protein types are represented by different symbols.