Bax induces activation of the unfolded protein response by inducing HAC1 mRNA splicing in Saccharomyces cerevisiae

Bax, a multidomain pro‐apoptotic Bcl‐2 protein, localizes to the endoplasmic reticulum (ER), where it regulates ER stress‐induced apoptosis. Adaptation to ER stress depends on the activation of an integrated signal transduction pathway known as the unfolded protein response (UPR). This study examined the death‐inducing activity of Bax and its ability to induce UPR signalling pathways in yeast. We observed that inhibition of global translation in yeast cells expressing Bax correlated with Bax‐induced cell death. Using a lacZ reporter containing several UPR cis‐activating regulatory elements, we also found that Bax directly activated the UPR. Furthermore, this correlated with the splicing of HAC1 mRNA, a gene involved in UPR activation. Bax induced expression of representative UPR target genes such as KAR2, DER1 and GCN4. Finally, we found that Ire1p function is critical for Bax‐induced cell death. Copyright © 2012 John Wiley & Sons, Ltd.