Fig. 2: PZ induces Bcl-xl degradation depending on the CRBN E3 ligase and proteasomes.

a No effect of ABT263 and/or the CRBN ligand pomalidomide (Poma) on Bcl-xl in WI38 NCs and IR-SCs. b-d ABT263, Poma and MG132 (a proteasome inhibitor) pretreatment blocked the degradation of Bcl-xl by PZ in WI38 NCs and IR-SCs, respectively. e CRBN knockout (KO) blocked Bcl-xl degradation by PZ in WI38 IR-SCs. f PZ, but not Bcl-xl-NP (an inactive form of PZ that cannot bind to CRBN), induced Bcl-xl degradation in NCs and IR-SCs. a–f Similar results were got in at least two independent experiments. g ABT263 and/or Poma did not induce cell death in NCs (left), while ABT263, but not Poma, induced cell death in IR-SCs (right). The data presented are mean value (n = 2 independent experiments). h Poma pretreatment blocked the effects of PZ on cell viability. Cells were pretreated with Poma for 1 h prior to PZ treatment, and cell viability in NCs (left) and IR-SCs (right) was measured 72 h after PZ treatment. The data presented are mean ± SEM (n = 3 independent experiments). a, b p < 0.0001 vs. control (CTL) and vehicle (VEH)-treated IR-SCs, respectively. i Knockout CRBN blocked the effects of PZ on cell viability. Cell viability was measured in wild-type (WT) and CRBN knockout (KO) IR-SCs 72 h after PZ treatment. The data presented are mean ± SEM (n = 3 independent experiments). a, b p < 0.0001 vs. VEH- and PZ-treated WT IR-SCs, respectively. j PZ (left), but not Bcl-xl-NP (right), effectively killed IR-SCs. The data presented are mean ± SEM (n = 3 independent experiments). a p < 0.0001, and b p = 0.0004 vs. NCs and IR-SCs treated with 1 μM PZ (left). a p = 0.0045 and b p = 0.0337 vs. NCs and IR-SCs treated with 1 μM Bcl-xl-NP (right), respectively. a–f Cells were pretreated with or without indicated compounds for 1 h and treated with PZ for 16 h. All statistical analyses presented were done by two-way ANOVA with Tukey’s post-hoc test. Source data are provided as a Source Data file.