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Gene Review

XBP1  -  X-box binding protein 1

Homo sapiens

Synonyms: TREB-5, TREB5, Tax-responsive element-binding protein 5, X-box-binding protein 1, XBP-1, ...
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Disease relevance of XBP1

  • After exposure to hypoxia, apoptosis increased and clonogenic survival decreased in XBP1-deficient cells [1].
  • Several recent studies have demonstrated that XBP-1 mRNA expression is associated with ERalpha status in breast tumors [2].
  • Overall, flaviviruses trigger the XBP1 signaling pathway and take advantage of this cellular response to alleviate virus-induced cytotoxicity [3].
  • Analysis in mouse insulinoma MIN6 cells revealed that methoxyflavones mildly activated the eukaryotic initiation factor 2alpha and nuclear factor erythroid 2-related factor pathways, but not the XBP1 pathway, and induced downstream genes, including glucose-regulated protein (GRP) 78, a molecular chaperone in the ER [4].
  • Identification of compounds that target the activity of IRE1 alpha/XBP-1 may yield novel therapies for the treatment of multiple myeloma and other malignancies that rely on an intact UPR [5].

Psychiatry related information on XBP1


High impact information on XBP1


Chemical compound and disease context of XBP1


Biological context of XBP1


Anatomical context of XBP1

  • XBP1 is required for the terminal differentiation of B lymphocytes into plasma cells, and IRE1 also participates in this differentiation event [15].
  • IRE1alpha-null MEFs, a cell line with a defective IRE1-XBP1 pathway, show elevated levels of HCV IRES-mediated translation [12].
  • 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 [12].
  • Whereas, in human tissues, weak splicing of XBP1 mRNA was detected only in the C1264R mutant, all rat thyroids including wild-type contained significant amounts of the spliced form of XBP1 as opposed to human liver and rat brain tissues, implying the existence of a previously unknown tissue-specific regulation of XBP1 processing [16].
  • BACKGROUND: Human X-box binding protein 1 (hXBP-1) is a transcription factor essential for hepatocyte growth as well as for plasma cell differentiation. hXBP-1 also binds to cis-elements of human T cell leukemia virus and human major histocompatibility complex genes [17].

Associations of XBP1 with chemical compounds


Physical interactions of XBP1

  • Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences [21].

Regulatory relationships of XBP1


Other interactions of XBP1

  • Key moleculars as XBP1 and GRP78/Bip were activated and up-regulated, which suggested the UPR pathway was activated [26].
  • HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA [27].
  • Key regulatory factors and their target genes are differentially expressed among these subgroups, including BCL-6, Blimp-1, and XBP1 [28].
  • In CHEC cells where Derlin-1 was down-regulated, increased expression of the immunoglobulin heavy chain-binding protein (Bip) and UPR-specific splicing of X-box DNAbinding protein 1 (XBP1) mRNA were detected, as compared with that in other tested cells, indicating that UPR was activated [29].
  • TREB7 and TREB36 protected all three repeats of the 21 bp, but TREB5 protected only the second repeat [30].

Analytical, diagnostic and therapeutic context of XBP1

  • A case-control study provides evidence of association for a functional polymorphism -197C/G in XBP1 to schizophrenia and suggests a sex-dependent effect [31].
  • We present microbiological growth assays for the UPR, reporter assays for UPR signaling, direct techniques to measure UPR activation in vivo, methods to study translation of HAC1 mRNA, and in vitro cleavage and ligation of HAC1 and XBP1 mRNA [32].
  • We have developed a new method to detect the spliced XBP1 mRNA by means of real-time PCR and we compared the result with measurements of the expression of the ER stress inducible gene BiP [22].
  • An electrophoretic mobility shift assay suggested that XBP1 does not directly bind to this sequence [25].
  • Here we examined the target genes of XBP1, using DNA microarray analysis in SH-SY5Y cells transfected with an XBP1-expressing vector [25].


  1. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Romero-Ramirez, L., Cao, H., Nelson, D., Hammond, E., Lee, A.H., Yoshida, H., Mori, K., Glimcher, L.H., Denko, N.C., Giaccia, A.J., Le, Q.T., Koong, A.C. Cancer Res. (2004) [Pubmed]
  2. Ligand-independent activation of estrogen receptor alpha by XBP-1. Ding, L., Yan, J., Zhu, J., Zhong, H., Lu, Q., Wang, Z., Huang, C., Ye, Q. Nucleic Acids Res. (2003) [Pubmed]
  3. Flavivirus Infection Activates the XBP1 Pathway of the Unfolded Protein Response To Cope with Endoplasmic Reticulum Stress. Yu, C.Y., Hsu, Y.W., Liao, C.L., Lin, Y.L. J. Virol. (2006) [Pubmed]
  4. Methoxyflavones protect cells against endoplasmic reticulum stress and neurotoxin. Takano, K., Tabata, Y., Kitao, Y., Murakami, R., Suzuki, H., Yamada, M., Iinuma, M., Yoneda, Y., Ogawa, S., Hori, O. Am. J. Physiol., Cell Physiol. (2007) [Pubmed]
  5. Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Lee, A.H., Iwakoshi, N.N., Anderson, K.C., Glimcher, L.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Kakiuchi, C., Iwamoto, K., Ishiwata, M., Bundo, M., Kasahara, T., Kusumi, I., Tsujita, T., Okazaki, Y., Nanko, S., Kunugi, H., Sasaki, T., Kato, T. Nat. Genet. (2003) [Pubmed]
  7. XBP1 gene polymorphism (-116C/G) and personality. Kato, C., Kakiuchi, C., Umekage, T., Tochigi, M., Kato, N., Kato, T., Sasaki, T. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2005) [Pubmed]
  8. Lack of support for a genetic association of the XBP1 promoter polymorphism with bipolar disorder in probands of European origin. Cichon, S., Buervenich, S., Kirov, G., Akula, N., Dimitrova, A., Green, E., Schumacher, J., Klopp, N., Becker, T., Ohlraun, S., Schulze, T.G., Tullius, M., Gross, M.M., Jones, L., Krastev, S., Nikolov, I., Hamshere, M., Jones, I., Czerski, P.M., Leszczynska-Rodziewicz, A., Kapelski, P., Bogaert, A.V., Illig, T., Hauser, J., Maier, W., Berrettini, W., Byerley, W., Coryell, W., Gershon, E.S., Kelsoe, J.R., McInnis, M.G., Murphy, D.L., Nurnberger, J.I., Reich, T., Scheftner, W., O'Donovan, M.C., Propping, P., Owen, M.J., Rietschel, M., Nöthen, M.M., McMahon, F.J., Craddock, N. Nat. Genet. (2004) [Pubmed]
  9. Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Reith, W., Satola, S., Sanchez, C.H., Amaldi, I., Lisowska-Grospierre, B., Griscelli, C., Hadam, M.R., Mach, B. Cell (1988) [Pubmed]
  10. A possible association between the [minus sign]116C/G single nucleotide polymorphism of the XBP1 gene and lithium prophylaxis in bipolar disorder. Masui, T., Hashimoto, R., Kusumi, I., Suzuki, K., Tanaka, T., Nakagawa, S., Kunugi, H., Koyama, T. Int. J. Neuropsychopharmacol. (2006) [Pubmed]
  11. pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response activator pXBP1(S) in mammalian ER stress response. Yoshida, H., Oku, M., Suzuki, M., Mori, K. J. Cell Biol. (2006) [Pubmed]
  12. Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response. Tardif, K.D., Mori, K., Kaufman, R.J., Siddiqui, A. J. Biol. Chem. (2004) [Pubmed]
  13. X-box binding protein 1 (XBP1) C--116G polymorphisms in bipolar disorders and age of onset. Hou, S.J., Yen, F.C., Cheng, C.Y., Tsai, S.J., Hong, C.J. Neurosci. Lett. (2004) [Pubmed]
  14. An analysis on transcriptional regulation activity of human XBP1 gene 5' upstream DNA sequences. Guo, F.J., Cheng, H.E., Yi, F.P., Peng, H.M., Song, F.Z. Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2006) [Pubmed]
  15. Birth pangs: the stressful origins of lymphocytes. Pillai, S. J. Clin. Invest. (2005) [Pubmed]
  16. Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism. Baryshev, M., Sargsyan, E., Wallin, G., Lejnieks, A., Furudate, S., Hishinuma, A., Mkrtchian, S. J. Mol. Endocrinol. (2004) [Pubmed]
  17. Upregulation and overexpression of human X-box binding protein 1 (hXBP-1) gene in primary breast cancers. Fujimoto, T., Onda, M., Nagai, H., Nagahata, T., Ogawa, K., Emi, M. Breast Cancer (2003) [Pubmed]
  18. Effect on tumor cells of blocking survival response to glucose deprivation. Park, H.R., Tomida, A., Sato, S., Tsukumo, Y., Yun, J., Yamori, T., Hayakawa, Y., Tsuruo, T., Shin-ya, K. J. Natl. Cancer Inst. (2004) [Pubmed]
  19. The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core. Clauss, I.M., Chu, M., Zhao, J.L., Glimcher, L.H. Nucleic Acids Res. (1996) [Pubmed]
  20. The X-box binding protein 1 (XBP1) gene is not associated with methamphetamine dependence. Morita, Y., Ujike, H., Tanaka, Y., Uchida, N., Nomura, A., Otani, K., Kishimoto, M., Morio, A., Inada, T., Harano, M., Komiyama, T., Yamada, M., Sekine, Y., Iwata, N., Iyo, M., Sora, I., Ozaki, N. Neurosci. Lett. (2005) [Pubmed]
  21. Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos. Ono, S.J., Liou, H.C., Davidon, R., Strominger, J.L., Glimcher, L.H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  22. Quantitative measurement of spliced XBP1 mRNA as an indicator of endoplasmic reticulum stress. Hirota, M., Kitagaki, M., Itagaki, H., Aiba, S. The Journal of toxicological sciences. (2006) [Pubmed]
  23. CD72-mediated suppression of human naive B cell differentiation by down-regulating X-box binding protein 1. Yamazaki, T., Nagumo, H., Hayashi, T., Sugane, K., Agematsu, K. Eur. J. Immunol. (2005) [Pubmed]
  24. Survival and proliferation factors of normal and malignant plasma cells. Klein, B., Tarte, K., Jourdan, M., Mathouk, K., Moreaux, J., Jourdan, E., Legouffe, E., De Vos, J., Rossi, J.F. Int. J. Hematol. (2003) [Pubmed]
  25. XBP1 induces WFS1 through an endoplasmic reticulum stress response element-like motif in SH-SY5Y cells. Kakiuchi, C., Ishiwata, M., Hayashi, A., Kato, T. J. Neurochem. (2006) [Pubmed]
  26. 1-Deoxymannojirimycin, the alpha1,2-mannosidase inhibitor, induced cellular endoplasmic reticulum stress in human hepatocarcinoma cell 7721. Lu, Y., Xu, Y.Y., Fan, K.Y., Shen, Z.H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  27. Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein response. Zheng, Y., Gao, B., Ye, L., Kong, L., Jing, W., Yang, X., Wu, Z., Ye, L. J. Microbiol. (2005) [Pubmed]
  28. The biology of human lymphoid malignancies revealed by gene expression profiling. Staudt, L.M., Dave, S. Adv. Immunol. (2005) [Pubmed]
  29. Overexpressed Derlin-1 Inhibits ER Expansion in the Endothelial Cells Derived from Human Hepatic Cavernous Hemangioma. Hu, D., Ran, Y.L., Zhong, X., Hu, H., Yu, L., Lou, J.N., Sun, L.X., Yang, Z.H. J. Biochem. Mol. Biol. (2006) [Pubmed]
  30. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. Yoshimura, T., Fujisawa, J., Yoshida, M. EMBO J. (1990) [Pubmed]
  31. 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. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  32. ER stress signaling by regulated splicing: IRE1/HAC1/XBP1. Back, S.H., Schröder, M., Lee, K., Zhang, K., Kaufman, R.J. Methods (2005) [Pubmed]
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