Figure 7.

Loss of DLC1 leads to proteasomal degradation of Bim and its binding partner, Mcl-1, and sensitizes cells to ABT-737-induced apoptosis. (A–D) HeLa (A) and 1205Lu (B) cells were transfected with control siRNA or siRNA specific to DLC1 24 h prior to 2 µM ABT-737 treatment as indicated. The MEK1/2 inhibitor UO126 (10 µM) was added at the time of siRNA transfection. Caspase-3-positive cells were identified by flow cytometry. Data (mean/SD) are representative of four independent experiments. (*) P < 0.05; (**) P < 0.01; (***) P < 0.001; (ns) nonsignificant (P > 0.05), two-tailed paired t-test. For Western blotting experiments, cells were treated with either 10 µM UO126 or 20 µM MG132 together with the indicated siRNAs in presence of 10 µM QVD, and cell lysates were prepared in 1% Triton lysis buffer. Results are representative of three independent experiments. The asterisk indicates the previous signal, probably from the small Mcl-1 isoform.