1: Biochem Biophys Res Commun. 2004 Jul 2;319(3):866-70. A case-control study provides evidence of association for a functional polymorphism -197C/G in XBP1 to schizophrenia and suggests a sex-dependent effect. Chen W, Duan S, Zhou J, Sun Y, Zheng Y, Gu N, Feng G, He L. Bio-X Life Science Research Center, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, PR China. Schizophrenia and bipolar disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. In order to test this hypothesis, we investigated a functional polymorphism -197C/G in XBP1, which was reported to increase the risk of bipolar disorder, in a case-control study (374 cases vs. 371 controls) to evaluate its genetic role in the pathogenesis of schizophrenia. In the present study, this polymorphism was found to be associated with schizophrenia both at allele (P=0.034; OR=1.26, 95% CI 1.02-1.55) and genotype levels (GG vs. CG+CC, 47.59% vs. 38.81%; P=0.016, df=1; OR=1.43, 95% CI 1.07-1.92). Our current data suggest that -197C/G in XBP1 is also a genetic risk factor for schizophrenia. In addition, it presents a sex-dependent genetic effect for the disorder. PMID: 15184063 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: Mol Cancer Ther. 2004 Apr;3(4):489-97. Induction of endoplasmic reticulum stress by ellipticine plant alkaloids. Hagg M, Berndtsson M, Mandic A, Zhou R, Shoshan MC, Linder S. Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute and Hospital, Stockholm, Sweden. Anticancer drugs often show complex mechanisms of action, including effects on multiple cellular targets. Detailed understanding of these intricate effects is important for the understanding of cytotoxicity. In this study, we examined apoptosis induction by ellipticines, a class of cytotoxic plant alkaloids known to inhibit topoisomerase II. The potent ellipticine derivative 6-propanamine ellipticine (6-PA-ELL) induced rapid apoptosis in MDA-MB-231 breast cancer cells, preceded by a conformational change in Bak and cytochrome c release. Experiments using knock-out mouse embryo fibroblasts established that Bak was of particular importance for cytotoxicity. 6-PA-ELL increased the expression of the endoplasmic reticulum chaperones GRP78/BiP and GRP94, suggesting induction of endoplasmic reticulum stress. Induction of GRP78 expression was dependent on the endoplasmic reticulum stress response element (ERSE) of the GRP78 promoter. Examination of different ellipticine derivatives revealed a correlation between pro-apoptotic activity and the ability to induce GRP78 expression. Furthermore, 6-PA-ELL was found to induce splicing of the mRNA encoding the XBP1 transcription factor, characteristic of endoplasmic reticulum stress, and to induce activation of the endoplasmic reticulum-specific caspase-12 in mouse colon cancer cells. We finally demonstrate that 6-PA-ELL induces apoptotic signaling also in enucleated cells, consistent with the existence of a cytoplasmic target for this compound. Our data suggest that induction of endoplasmic reticulum stress may contribute to the cytotoxicity of ellipticines. PMID: 15078993 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Biochem Biophys Res Commun. 2004 Apr 30;317(2):390-6. Discordance of UPR signaling by ATF6 and Ire1p-XBP1 with levels of target transcripts. Shang J, Lehrman MA. Department of Pharmacology, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9041, USA. Accumulation of misfolded proteins within the lumen of the mammalian endoplasmic reticulum (ER) activates the unfolded protein response (UPR). ATF6 and Ire1p are ER-associated proteins that control UPR-specific transcription systems in mammals; UPR signaling involves cleavage of ATF6 and splicing of XBP1 mRNA initiated by Ire1p. We tested the hypothesis that activation of ATF6 and/or Ire1p determines the levels of mRNAs derived from target genes encoding GRP78/BiP and EDEM. By subjecting dermal fibroblasts to multiple stresses, strong correlations were found between ATF6 activation and XBP1 splicing, and between GRP78/BiP mRNA and EDEM mRNA accumulation. Surprisingly, there was no reasonable correlation between activation of either signal transducer with accumulation of either target transcript. Thus, ATF6 and Ire1p signaling do not define the magnitude of UPR-dependent mRNA increases, even though they may be necessary for gene activation, suggesting the existence of additional stress-sensitive factors acting as "coincidence detectors" for transcript accumulation. PMID: 15063770 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: Genes Cells. 2004 Mar;9(3):261-70. The endoplasmic reticulum stress response is stimulated through the continuous activation of transcription factors ATF6 and XBP1 in Ins2+/Akita pancreatic beta cells. Nozaki J, Kubota H, Yoshida H, Naitoh M, Goji J, Yoshinaga T, Mori K, Koizumi A, Nagata K. Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan. The dominant C96Y mutation of one of the two murine insulin genes, Ins2, causes diabetes mellitus in 'Akita' mice. Here we established pancreatic islet beta cell lines from heterozygous mice (Ins2+/Akita). Western blot analysis of endoplasmic reticulum (ER) molecular chaperones indicated that Grp78, Grp94 and Orp150 are significantly increased in Ins2+/Akita cells compared with wild-type (Ins2+/+) cells. Reporter gene assays using the human GRP78 promoter with or without the ER stress response element (ERSE) showed that Ins2+/Akita cells exhibit significantly stronger ERSE-dependent transcriptional activity than Ins2+/+ cells. Transient over-expression of the Ins2 C96Y mutant in wild-type beta cells induces a stronger ERSE-dependent stress response than does wild-type Ins2 over-expression. The ERSE-binding transcription factor ATF6 is strongly activated in Ins2+/Akita cells. The activity of a reporter containing the specific binding sequence of another ERSE-binding transcription factor, XBP1, is also enhanced in Ins2+/Akita cells. Levels of active forms of XBP1 mRNA and protein are both markedly elevated in Ins2+/Akita cells. These results indicate that this cell line is subject to continuous ER stress and that the Ins2 C96Y mutation induces the expression of ER chaperones through the activation of ATF6 and XBP1. PMID: 15005713 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 5: J Biol Chem. 2004 Apr 23;279(17):17158-64. Epub 2004 Feb 11. Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response. Tardif KD, Mori K, Kaufman RJ, Siddiqui A. Department of Microbiology and Program in Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Hepatitis C virus (HCV) gene expression disrupts normal endoplasmic reticulum (ER) functions and induces ER stress. ER stress results from the accumulation of unfolded or misfolded proteins in the ER; cells can alleviate this stress by degrading or refolding these proteins. The IRE1-XBP1 pathway directs both protein refolding and degradation in response to ER stress. Like IRE1-XBP1, other branches of the ER stress response mediate protein refolding. However, IRE1-XBP1 can also specifically activate protein degradation. We show here that XBP1 expression is elevated in cells carrying HCV subgenomic replicons, but XBP1 trans-activating activity is repressed. This prevents the IRE1-XBP1 transcriptional induction of EDEM (ER degradation-enhancing alpha-mannosidase-like protein). The mRNA expression of EDEM is required for the degradation of misfolded proteins. Consequently, misfolded proteins are stable in cells expressing HCV replicons. HCV may suppress the IRE1-XBP1 pathway to stimulate the synthesis of its viral proteins. IRE1alpha-null MEFs, a cell line with a defective IRE1-XBP1 pathway, show elevated levels of HCV IRES-mediated translation. Therefore, HCV may suppress the IRE1-XBP1 pathway to not only promote HCV expression but also to contribute to the persistence of the virus in infected hepatocytes. PMID: 14960590 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 6: J Neurochem. 2004 Feb;88(4):983-92. Brain trauma induces X-box protein 1 processing indicative of activation of the endoplasmic reticulum unfolded protein response. Paschen W, Yatsiv I, Shoham S, Shohami E. Laboratory of Molecular Nurology, Max-Planck-Institute for Neurological Research, Koeln, Germany. paschen@mpin-koeln.mpg.de Brain trauma was induced in mice using a closed head injury (CHI) model. At 1, 6 or 24 h after trauma, brains were dissected into the cortex, striatum and hippocampus. Changes in levels of processed X-box protein 1 (xbp1), glucose-regulated protein 78 (grp78), growth arrest and DNA damage-inducible gene 153 (gadd153) and heat-shock protein 70 (hsp70) mRNA, indicating impaired endoplasmic reticulum (ER) and cytoplasmic functioning, were evaluated by quantitative PCR. In the cortex, processed xbp1 mRNA levels rose to 2000% of control 1 h after CHI, and stayed high throughout the experiments. In the hippocampus and striatum, processed xbp1 mRNA levels rose in a delayed fashion, peaking at 6 h (1000% of control) and 24 h after CHI (1500% of control) respectively. Levels of grp78 mRNA were only slightly increased in the cortex 24 h after CHI (150% of control), and were unchanged or transiently decreased in the hippocampus and striatum. Levels of gadd153 mRNA did not change significantly after trauma. A transient rise in hsp70 mRNA levels was observed only in the cortex, peaking at 1 h after CHI (600% of control). Processing of xbp1 mRNA is a sign of activation of the unfolded protein response indicative of ER dysfunction. The results suggest that brain trauma induces ER dysfunction, which spreads from the ipsilateral cortex to the hippocampus and striatum. These observations may have clinical implications and should therefore be considered for future investigations on therapeutic intervention of brain injury caused by contusion-induced neurotrauma. PMID: 14756820 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 7: J Biol Chem. 2004 Apr 2;279(14):13953-61. Epub 2004 Jan 12. Gene expression changes associated with the endoplasmic reticulum stress response induced by microsomal cytochrome p450 overproduction. Szczesna-Skorupa E, Chen CD, Liu H, Kemper B. Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. Induction of drug-metabolizing microsomal cytochromes p450 (p450s) results in a striking proliferation of the smooth endoplasmic reticulum (ER). Overexpression of P450s in yeast and cultured cells produces a similar response. The signals mediating this process are not known but probably involve signal transduction pathways involved in the unfolded protein response (UPR) or the ER overload response (EOR). We have examined the temporal response of specific genes in these pathways and genes globally to overexpression of p450 in cultured cells. Activity of NFkappaB, an EOR component, was substantially increased by overexpression of full-length p450 2C2 or a chimera with the 28-amino acid signal anchor sequence of p450 2C2 in HepG2 cells, and the activation correlated temporally with the accumulation of p450 in the cells. In the UPR pathway, activation of the transcription factor XBP1 by IRE1 also correlated with the accumulation of p450 in the cells, and in contrast, maximum activation of the BiP/grp78 promoter preceded the accumulation. Differential effects of expression of p450 on apoptosis were observed in nonhepatic COS1 and hepatic HepG2 cells. In COS1 cells, apoptosis was induced, and this correlated with sustained activation of the pro-apoptotic JNK pathway, induction of CHOP, and an absence of the increased NFkappaB activity. In HepG2 cells, JNK was only transiently activated, and CHOP expression was not induced. As assessed by DNA microarray analysis, up-regulation of signaling genes was predominant including those involved in anti-apoptosis and ER stress. These results suggest that both the EOR and UPR pathways are involved in the cellular response to induction of p450 expression and that in hepatic cells genes are also induced to block apoptosis, which may be a physiologically relevant response to prevent cell death during xenobiotic induced expression of p450 in the liver. PMID: 14718536 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 8: J Hepatol. 2003 May;38(5):605-14. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. Shuda M, Kondoh N, Imazeki N, Tanaka K, Okada T, Mori K, Hada A, Arai M, Wakatsuki T, Matsubara O, Yamamoto N, Yamamoto M. Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan. BACKGROUND/AIMS: We identified the glucose-regulated protein (grp) 78 as a transformation-associated gene in hepatocellular carcinoma (HCC). Grp78 is a molecular chaperone involved in the unfolded protein response, the expression of which can be regulated by the transcription factors ATF6 and XBP1. Thus, we investigated the regulatory mechanisms of the grp78 gene in liver malignancy. METHODS: Expression of grp78, ATF6 and XBP1 was examined by Northern blot, RT-PCR, immunoblot and immunohistochemical analyses. A reporter assay of the grp78 promoter was also performed. RESULTS: Elevation of grp78 and ATF6 mRNAs and the splicing of XBP1 mRNA, resulting in the activation of XBP1 product, occurred in HCC tissues with increased histological grading. Higher accumulation of the grp78 product in the cytoplasm, concomitantly with marked nuclear localization of the activated ATF6 product (p50ATF6), was observed in moderately to poorly differentiated HCC tissues. Cooperation between the distal DNA segment and the proximal endoplasmic reticulum stress response elements was essential for maximum transcription of the grp78 promoter in HCC cells. CONCLUSIONS: The endoplasmic reticulum stress pathway mediated by ATF6 and by IRE1-XBP1 systems seems essential for the transformation-associated expression of the grp78 gene in HCCs. PMID: 12713871 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 9: J Cereb Blood Flow Metab. 2003 Apr;23(4):449-61. Transient cerebral ischemia activates processing of xbp1 messenger RNA indicative of endoplasmic reticulum stress. Paschen W, Aufenberg C, Hotop S, Mengesdorf T. Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Gleuelerstr. 50, 50931 Koln, Germany. paschen@mpin-koeln.mpg.de Cells respond to conditions associated with endoplasmic reticulum (ER) dysfunction with activation of the unfolded protein response, characterized by a shutdown of translation and induction of the expression of genes coding for ER stress proteins. The genetic response is based on IRE1-induced processing of xbp1 messenger RNA (mRNA), resulting in synthesis of new XBP1proc protein that functions as a potent transcription factor for ER stress genes. xbp1 processing in models of transient global and focal cerebral ischemia was studied. A marked increase in processed xbp1 mRNA levels during reperfusion was observed, most pronounced (about 35-fold) after 1-h occlusion of the right middle cerebral artery. The rise in processed xbp1 mRNA was not paralleled by a similar increase in XBP1proc protein levels because transient ischemia induces severe suppression of translation. As a result, mRNA levels of genes coding for ER stress proteins were only slightly increased, whereas mRNA levels of heat-shock protein 70 rose about 550-fold. Under conditions associated with ER dysfunction, cells require activation of the entire ER stress-induced signal transduction pathway, to cope with this severe form of stress. After transient cerebral ischemia, however, the block of translation may prevent synthesis of new XBP1proc protein and thus hinder recovery from ischemia-induced ER dysfunction. PMID: 12679722 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 10: J Biol Chem. 2003 May 23;278(21):19367-77. Epub 2003 Feb 21. Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. Holtz WA, O'Malley KL. Anatomy and Neurobiology Department, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Genes associated with Parkinson's disease (PD) have suggested a role for ubiquitin-proteasome dysfunction and aberrant protein degradation in this disorder. Inasmuch as oxidative stress has also been implicated in PD, the present study examined transcriptional changes mediated by the Parkinsonism-inducing neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) in a dopaminergic cell line. Microarray analysis of RNA isolated from toxin treated samples revealed that the stress-induced transcription factor CHOP/Gadd153 was dramatically up-regulated by both 6-OHDA and MPP+. Treatment with 6-OHDA also induced a large number of genes involved in endoplasmic reticulum stress and unfolded protein response (UPR) such as ER chaperones and elements of the ubiquitin-proteasome system. Reverse transcription-PCR, Western blotting, and immunocytochemical approaches were used to quantify and temporally order the UPR pathways involved in neurotoxin-induced cell death. 6-OHDA, but not MPP+, significantly increased hallmarks of UPR such as BiP, c-Jun, and processed Xbp1 mRNA. Both toxins increased the phosphorylation of UPR proteins, PERK and eIF2 alpha, but only 6-OHDA increased phosphorylation of c-Jun. Thus, 6-OHDA is capable of triggering multiple pathways associated with UPR, whereas MPP+ exhibits a more restricted response. The involvement of UPR in these widely used neurotoxin models supports the role of ubiquitin-proteasome pathway dysfunction in PD. PMID: 12598533 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 11: Dev Cell. 2003 Feb;4(2):265-71. Comment in: Dev Cell. 2003 Feb;4(2):144-6. A time-dependent phase shift in the mammalian unfolded protein response. Yoshida H, Matsui T, Hosokawa N, Kaufman RJ, Nagata K, Mori K. Graduate School of Biostudies, Kyoto University, Kyoto 606-8304, Japan. Unfolded or misfolded proteins in the endoplasmic reticulum (ER) must be refolded or degraded to maintain homeostasis of the ER. The ATF6 and IRE1-XBP1 pathways are important for the refolding process in mammalian cells; activation of these transcriptional programs culminates in induction of ER-localized molecular chaperones and folding enzymes. We show here that degradation of misfolded glycoprotein substrates requires transcriptional induction of EDEM (ER degradation-enhancing alpha-mannosidase-like protein), and that this is mediated specifically by IRE1-XBP1 and not by ATF6. As XBP1 is produced after ATF6 activation, our results reveal a time-dependent transition in the mammalian unfolded protein response: an ATF6-mediated unidirectional phase (refolding only) is followed by an XBP1-mediated bidirectional phase (refolding plus degradation) as the response progresses. PMID: 12586069 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 12: Cell Calcium. 2003 Feb;33(2):83-9. Loading neurons with BAPTA-AM activates xbp1 processing indicative of induction of endoplasmic reticulum stress. Paschen W, Hotop S, Aufenberg C. Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Gleuelerstr 50, Cologne 50931, Koln, Germany. paschen@mpin.mphg.de Loading cells with the calcium chelator BAPTA-AM is an analytical tool which has been used to suppress a rise in cytoplasmic calcium activity under various experimental conditions and thus, to evaluate the role of elevated cytoplasmic calcium levels in the process under investigation. BAPTA-AM may, however, not only have an isolated effect on cytoplasmic processes but also on functions of other subcellular compartments such as the endoplasmic reticulum (ER). Under conditions associated with ER dysfunction, the unfolded protein response is activated which is characterized by suppression of translation and processing of xbp1 mRNA, resulting in activation of the expression of genes coding for ER stress proteins. To investigate whether BAPTA-AM causes ER stress, primary neuronal cell cultures were loaded with varying amounts of BAPTA-AM. Exposure of cells to BAPTA-AM induced a marked rise in processed xbp1 mRNA levels, correlating with exposure times and BAPTA-AM concentrations in the medium used for loading. The increase in processed xbp1 mRNA was associated with suppression of protein synthesis and induction of cell injury. The results of this study indicate that loading primary neuronal cell cultures with BAPTA-AM activates xbp1 processing, implying that this calcium chelator does not have an isolated effect on cytoplasmic calcium activity but also an affect on ER function. PMID: 12531184 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 13: Brain Res Mol Brain Res. 2002 Aug 15;104(2):227-39. Genes associated with pro-apoptotic and protective mechanisms are affected differently on exposure of neuronal cell cultures to arsenite. No indication for endoplasmic reticulum stress despite activation of grp78 and gadd153 expression. Mengesdorf T, Althausen S, Paschen W. Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Gleuelerstrasse 50, Cologne, Germany. The effect of arsenite exposure on cell viability, protein synthesis, energy metabolism and the expression of genes coding for cytoplasmic (hsp70) and endoplasmic reticulum (ER; gadd153, grp78, grp94) stress proteins was investigated in primary neuronal cell cultures. Furthermore, signs of ER stress were evaluated by investigating xbp1 mRNA processing. Arsenite levels of 30 and 100 microM induced severe cell injury. Protein synthesis was reduced to below 20% of control in cultures exposed to 30 and 100 microM arsenite for 1 h, and it remained markedly suppressed until 24 h of exposure. Arsenite induced a transient inhibition of energy metabolism after 1 h of exposure, but energy state recovered completely after 3 h. Arsenite exposure affected the expression and translation of genes coding for HSP70 and GRP78, GRP94, GADD153 to different extents. While hsp70 mRNA levels rose drastically, approximally 550-fold after 6 h exposure, HSP70 protein levels did not change over the first 6 h. On the other hand, gadd153 mRNA levels rose only approximately 14-fold after 6 h exposure, while GADD153 protein levels were markedly increased after 3 and 6 h exposure. HSP70 protein levels were markedly increased and GADD153 protein levels decreased to almost control levels in cultures left in arsenite solution for 24 h, i.e. when only a small fraction of cells had escaped arsenite toxicity. Arsenite exposure of neurons thus induced an imbalance between pro-apoptotic and survival-activating pathways. Despite the marked increase in gadd153 mRNA levels, we did not observe signs of xbp1 processing in arsenite exposed cultures, indicating that arsenite did not produce ER stress. PMID: 12225878 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 14: Genes Dev. 2002 Feb 15;16(4):452-66. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, Yoshida H, Mori K, Kaufman RJ. Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. All eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded protein response (UPR). In yeast, a type-I ER transmembrane protein kinase, Ire1p, is the proximal sensor of unfolded proteins in the ER lumen that initiates an unconventional splicing reaction on HAC1 mRNA. Hac1p is a transcription factor required for induction of UPR genes. In higher eukaryotic cells, the UPR also induces site-2 protease (S2P)-mediated cleavage of ER-localized ATF6 to generate an N-terminal fragment that activates transcription of UPR genes. To elucidate the requirements for IRE1alpha and ATF6 for signaling the mammalian UPR, we identified a UPR reporter gene that was defective for induction in IRE1alpha-null mouse embryonic fibroblasts and S2P-deficient Chinese hamster ovary (CHO) cells. We show that the endoribonuclease activity of IRE1alpha is required to splice XBP1 (X-box binding protein) mRNA to generate a new C terminus, thereby converting it into a potent UPR transcriptional activator. IRE1alpha was not required for ATF6 cleavage, nuclear translocation, or transcriptional activation. However, ATF6 cleavage was required for IRE1alpha-dependent induction of UPR transcription. We propose that nuclear-localized IRE1alpha and cytoplasmic-localized ATF6 signaling pathways merge through regulation of XBP1 activity to induce downstream gene expression. Whereas ATF6 increases the amount of XBP1 mRNA, IRE1alpha removes an unconventional 26-nucleotide intron that increases XBP1 transactivation potential. Both processing of ATF6 and IRE1alpha-mediated splicing of XBP1 mRNA are required for full activation of the UPR. PMID: 11850408 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 15: Nucleic Acids Res. 1990 Sep 25;18(18):5578. BanI polymorphism at the XBP1 locus. Fontaine B, Hanson MP, Liou HC, Glimcher LH, Rouleau GA, Gusella JF. Molecular Neurogenetics Laboratory, Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Boston 02114. PMID: 1977120 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------