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.
Biotechnology Center for Agriculture and the Environment, Department of Plant Biology and Pathology, Cook College, Rutgers University, New Brunswick, NJ, USA. birsencakir@hotmail.com
Birsen
B
Cakir
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D056811:Unfolded Protein Response; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; C494828:Bax protein, rat; C091341:HAC1 protein, S cerevisiae; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051028:bcl-2-Associated X Protein