Cyclin D1 activates the UPR pro-apoptotic pathway after bortezomib treatment. Cells were treated with bortezomib (B, 5 or 10 nM) or vehicle (control) for 24 h. The expression of the CHOP (A), BiP and GRP94 (B) genes was determined by RT quantitative-PCR. For each series, the mean of triplicate samples is presented, together with the SD. All experiments were carried out three times. *p < 0.05, **p < 0.01. C. Cells were treated as described above. Proteins were blotted on membranes and probed with an anti-caspase 4 Ab. The anti-GAPDH Ab was used as a loading control. D. Cells were treated with a caspase 4 inhibitor (Z-LEVD, 1 μM) for 1 h, and then with vehicle or bortezomib (7.5 nM for 8226 or 10 nM LP1, respectively) for another 24 h. Cell viability was estimated in MTT assays. *p < 0.05.