title: BCL-2 modulates the unfolded protein response by enhancing splicing of X-box binding protein-1.
abstract: Accumulation of unfolded proteins within the endoplasmic reticulum (ER) triggers a highly conserved stress response mechanism termed the unfolded protein response (UPR). The UPR is a complex series of signaling pathways controlled by ER localized transmembrane receptors, PERK, ATF6 and IRE1α. Following activation IRE1α splices XBP-1 mRNA facilitating the formation of a potent transcription factor, spliced XBP-1. The BCL-2 family members, BAX and BAK, in addition to the mitochondrion also localize to the ER and have been demonstrated to directly interact with IRE1α promoting its activity. In this study we show that in addition to BAX and BAK, the anti-apoptotic BCL-2 protein can regulate IRE1α activity. Enhanced splicing of XBP-1 was observed in BCL-2 overexpressing cells implicating BCL-2 in the complex regulation of IRE1α activity.
authors: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors: Triona Ni
authors: TN
authors: Chonghaile
authors: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Medicine, National University of Ireland, Galway, Ireland.
authors: Sanjeev
authors: S
authors: Gupta
authors: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors: Mohan
authors: M
authors: John
authors: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors: Eva
authors: E
authors: Szegezdi
authors: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland. Electronic address: susan.logue@nuigalway.ie.
authors: Susan E
authors: SE
authors: Logue
authors: Apoptosis Research Centre, National University of Ireland, Galway, Ireland; School of Natural Sciences, National University of Ireland, Galway, Ireland. Electronic address: afshin.samali@nuigalway.ie.
authors: Afshin
authors: A
authors: Samali
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004722:Endoribonucleases / Q000032:analysis / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000032:analysis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D012326:RNA Splicing; D051381:Rats; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; C575026:Ern1 protein, rat; D009097:Multienzyme Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C000605545:Xbp1 protein, rat; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Apoptosis; BCL-2; ER stress; Unfolded protein response; XBP-1