Fig. 4: Identification of exosome-dependent itaconated secreted proteins by PBSP.

a Schematic of PBSP profiling under normal and exosome inhibition conditions. The exosome inhibitor GW4869 was used to block exosome secretion, reducing the enrichment of exosome-dependent itaconated secreted proteins. Created in BioRender. Chu, l. (2025) https://BioRender.com/wudkzfu. b Volcano plot showing the comparative enrichment of proteins between normal and exosome inhibition conditions. Exosome-dependent itaconated secreted proteins are highlighted in red. p-values were determined by two-sided Student t-tests. c Proportion of known exosome proteins within the exosome-dependent itaconated secreted proteins. d Enrichment ratios of exosome-dependent itaconated proteins (GSDMD) and exosome-independent itaconated proteins (LDHA) under normal and exosome inhibition conditions. p-values: 0 (GSDMD), 0.01300 (LDHA). e Gene Ontology (GO) biological process analysis of the exosome-dependent itaconated secreted proteins identified by PBSP with one-sided p-values from Fisher’s Exact test. f Enrichment ratios of four components of the COP9 signalosome complex (CSN). p-values: 0.01396 (COPS2), 0.02366 (COPS3), 0.00364 (COPS3), 0 (COPS7A). g Enrichment ratios of representative proteins involved in apoptosis, including CDK1, CDK6, and CDK7, under normal and exosome inhibition conditions. p-values: 0.04851 (CDK1), 0.01117 (CDK7), 0 (CDK6). N.D., not determined. In (d, f, g), the error bars show mean ± SD from three biological replicates. *p < 0.05, ***p < 0.001 (two sided Student’s t-test). h KEGG analysis of 204 novel itaconated proteins in the exosome-dependent itaconated secreted proteins with one-sided p-values from Fisher’s Exact test.