Fig. 4

CRL substrate evaluation by proteomics profiling of bortezomib effects in CNDT2 SI-NET cells. a Venn diagram showing identification overlap in CNDT2 cells between proteomics profiling of pevonedistat effects (as described in Fig. 3) and bortezomib effects (top), and scatterplot indicating proteins found to be stabilized by monotherapy with pevonedistat and/or bortezomib (bottom). b Vulcano plot showing protein-level regulation in response to bortezomib treatment of CNDT2 cells. Indicated in the plot are proteins also found to be stabilized by pevonedistat treatment in CNDT2 cells (blue) or both CNDT2 cells and HC45 cells (red) as described in Fig. 3. c Scatterplot showing CNDT2 cells’ protein-level regulation in response to bortezomib treatment alone or in combination with pevonedistat. Dashed line indicate 99th percentile of the comparison between effects after treatment with bortezomib/pevonedistat combination and bortezomib alone. Pink area indicate proteins that are stabilized to a higher degree after combination treatment. d Western blotting showing p27 levels in response to treatment of CNDT2 cells with bortezomib and pevonedistat alone or in combination. The barplot indicates relative protein levels normalized to GAPDH. Western blotting quantification was based on three independent experiments with barplot error bars indicating SD and p-values calculated by Student’s t-test. e Barplot showing the 30 SI-NET CRL substrate candidates that were stabilized more in response to bortezomib pevonedistat combination than bortezomib alone in CNDT2 cells. Indicated in green are proteins defined as tumor suppressors (TSG) in COSMIC