title: Functional characterization of the ER stress induced X-box-binding protein-1 (Xbp-1) in the porcine system.
abstract: BACKGROUND
  The unfolded protein response (UPR) is an evolutionary conserved adaptive reaction for increasing cell survival under endoplasmic reticulum (ER) stress conditions. X-box-binding protein-1 (Xbp1) is a key transcription factor of UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The UPR induced by ER stress was extensively studied in diseases linked to protein misfolding and aggregations. However, in the porcine system, genes in the UPR pathway were not investigated. In this study, we isolated and characterized the porcine Xbp1 (pXbp1) gene in ER stress using porcine embryonic fibroblast (PEF) cells and porcine organs. ER stress was induced by the treatment of tunicamycin and cell viability was investigated by the MTT assay. For cloning and analyzing the expression pattern of pXbp1, RT-PCR analysis and Western blot were used. Knock-down of pXbp1 was performed by the siRNA-mediated gene silencing.
  
  
  RESULTS
  We found that the pXbp1 mRNA was the subject of the IRE1α-mediated unconventional splicing by ER stress. Knock-down of pXbp1 enhanced ER stress-mediated cell death in PEF cells. In adult organs, pXbp1 mRNA and protein were expressed and the spliced forms were detected.
  
  
  CONCLUSIONS
  It was first found that the UPR mechanisms and the function of pXbp1 in the porcine system. These results indicate that pXbp1 plays an important role during the ER stress response like other animal systems and open a new opportunity for examining the UPR pathway in the porcine model system.
authors: Aging Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors: Jin-Yu
authors: JY
authors: Zhang
authors: Kyu-Sun
authors: KS
authors: Lee
authors: Ji-Su
authors: JS
authors: Kim
authors: Bong-Seok
authors: BS
authors: Song
authors: Dong-Il
authors: DI
authors: Jin
authors: Deog-Bon
authors: DB
authors: Koo
authors: Kweon
authors: K
authors: Yu
references: Nat Immunol. 2000 Aug;1(2):163-8
references: 11248810
references: Xenotransplantation. 2006 Nov;13(6):488-99
references: 17059572
references: Genes Dev. 2000 Jan 15;14(2):152-7
references: 10652269
references: ILAR J. 2006;47(3):243-58
references: 16804199
references: Mol Cell Biol. 2003 Nov;23(21):7448-59
references: 14559994
references: J Cell Biol. 2006 Feb 13;172(4):565-75
references: 16461360
references: PLoS Biol. 2006 Nov;4(11):e374
references: 17090218
references: Cell Death Differ. 2004 Apr;11(4):381-9
references: 14685163
references: Biochem Biophys Res Commun. 1999 Aug 2;261(2):350-6
references: 10425189
references: Mol Cell. 2001 Jun;7(6):1153-63
references: 11430819
references: Nucleic Acids Res. 2010 Oct;38(18):6265-73
references: 20507909
references: J Clin Invest. 2008 Apr;118(4):1571-7
references: 18324337
references: Cell. 1986 Jul 18;46(2):291-300
references: 3087629
references: Science. 2000 Jan 28;287(5453):664-6
references: 10650002
references: Comp Med. 2006 Feb;56(1):35-45
references: 16521858
references: Nat Med. 2004 Jan;10(1):98-102
references: 14702639
references: Annu Rev Biochem. 2005;74:739-89
references: 15952902
references: Nature. 1985 Jun 20-26;315(6021):680-3
references: 3892305
references: Cell. 2001 Dec 28;107(7):881-91
references: 11779464
references: Science. 2002 Feb 8;295(5557):1089-92
references: 11778012
references: Biochem J. 2002 Sep 1;366(Pt 2):585-94
references: 12014989
references: EMBO J. 2005 Dec 21;24(24):4368-80
references: 16362047
references: Cell Metab. 2009 Jun;9(6):556-64
references: 19490910
references: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9946-51
references: 12902539
references: PLoS One. 2010 May 05;5(5):e10489
references: 20463975
references: Cell Death Differ. 2006 Mar;13(3):374-84
references: 16397578
references: Trends Biochem Sci. 1997 Apr;22(4):132-7
references: 9149533
references: Mol Biol Cell. 1999 Nov;10(11):3787-99
references: 10564271
references: Nature. 2000 Sep 7;407(6800):86-90
references: 10993078
references: Cell Death Differ. 2006 Mar;13(3):363-73
references: 16397583
references: BMC Genomics. 2005 May 10;6:70
references: 15885146
references: Nature. 2001 Jul 19;412(6844):300-7
references: 11460154
references: Nat Rev Mol Cell Biol. 2007 Jul;8(7):519-29
references: 17565364
references: Nature. 2002 Jan 3;415(6867):92-6
references: 11780124
references: Nat Biotechnol. 2002 Mar;20(3):251-5
references: 11875425
references: Annu Rev Biochem. 1987;56:497-534
references: 3304143
references: Mol Cell. 2000 May;5(5):897-904
references: 10882126