Fig. 6: Loss of USP18 switches IFN-induced apoptosis to pyroptosis by altering the ISG landscape.
From: Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis
a Reactome analysis of commonly enhanced genes in IFNα treated USP18−/− THP-1 and MDA-MB-231 cells. p-value was determined by two-sided binomial test adjusted with Benjamini–Hochberg approach. b IL-1β secretions and cleaved IL-1β in culture supernatant were analyzed in MDA-MB-231 WT and USP18−/− cells with or without IFNα (1000 U/ml) for 36 h (n = 3 independent samples each). c Percentage of live WT, USP18+/− and USP18−/− THP-1 cells treated with or without IFNα (1000 U/ml) for 48 h (n = 3 independent samples each). d LDH release assay and MFI of surface-exposed calreticulin (ecto-CRT) of WT, USP18+/− and USP18−/− cells with or without IFNα (1000U/ml) for 48 h (n = 3 independent samples each). e Western blot analysis of WT and USP18−/− THP-1 cells treated with or without IFNα (1000U/ml) for 36 h (lane 1–4) or WT cells treated with staurosporine for 24 h (lanes 5, 6). f Percentage of live WT and USP18−/− THP-1 cells pre-treated with mock or Necrostatin-1 (10 μM) for 6 h, then treated with IFNα (1000 U/ml) for the indicated times (n = 3 independent samples each). g Western blot analysis of THP-1 cells (WT, USP18+/− and USP18−/−) and MDA-MB-231 cells (WT and USP18−/−) treated with or without IFNα for 36 h. h Western blot analysis of WT and USP18+/− THP-1 cells treated with or without IFNα for 72 h. i Western blot of sorted GFP+Lin−c-Kit+ splenocytes from Usp18+/f and Usp18+/Δ AE9a recipient mice (Usp18+/f n = 3, Usp18+/Δ n = 3 mice). j MFI of ecto-CRT of sorted GFP+Lin−c-Kit+ splenocytes from Usp18+/f and Usp18+/Δ AE9a recipient mice (Usp18+/f n = 3, Usp18+/Δ n = 3 mice). p-value was determined by two-tailed Student t-test. k LDH release assay of Usp18+/f and Usp18+/Δ AE9a cells after 48 h of treatment with or without murine IFNβ (500U/ml) (n = 3 independent samples each). l Analysis of IL-1β secretions of culture supernatant from (k). All data represent mean ± s.d, except where indicated. n.s. = not statistically significant. p-value for (b–d, f, and k, l was determined by one-way ANOVA test. Source data are provided as a Source Data file.
