Fig. 1

The cytotoxic effects of proteasomal inhibition are SETD2/H3K36Me3-dependent. A Effect of proteasome inhibition by bortezomib (bort), carfilzomib (carf) and ixazomib (ixa) on SETD2 and H3K36Me3 levels in HMC-1.1, HMC-1.2 and ROSA^{KIT D816V}. B Reduction of clonogenic growth of HMC-1.1 and -1.2 cells in the presence of increasing doses of bortezomib, carfilzomib and ixazomib. All the clonogenic survival rates are expressed as mean ± standard deviation of counts from three independent experiments. C Induction of apoptosis in HMC-1.1 and -1.2 cells after 24 h-incubation with 10 nM bortezomib, 5 nM carfilzomib and 50 nM ixazomib. Each column represents the mean of three independent experiments and the bars represent the standard error. D Reduction of SETD2 expression and H3K36Me3 after 24, 48 and 72 h of SETD2 depletion by siRNA. E Reduction of clonogenic growth of control and SETD2 RNAi-depleted ROSA^{KIT D816V} cells in the presence of increasing doses of bortezomib, carfilzomib and ixazomib. F Induction of apoptosis in control and SETD2 RNAi-depleted ROSA^{KIT D816V} cells after 24 h-incubation with 10 nM bortezomib, 5 nM carfilzomib and 50 nM ixazomib