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Gene Review

Xbp1  -  X-box binding protein 1

Mus musculus

Synonyms: D11Ertd39e, TREB-5, TREB5, Tax-responsive element-binding protein 5, Treb5, ...
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Disease relevance of Xbp1


High impact information on Xbp1

  • Mammalian XBP-1 is essential for immunoglobulin secretion and development of plasma cells, and high levels of XBP-1 messenger RNA are found in specialized secretory cells [6].
  • IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA [6].
  • Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres [7].
  • XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium [7].
  • Furthermore, the absence of a specific X box binding protein in patients with severe combined immunodeficiency disease whose cells lack class II suggests an important role for these proteins in class II regulation [8].

Biological context of Xbp1

  • By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1 [9].
  • Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells [9].
  • In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis [9].
  • XBP1 induces certain ER-targeted proteins, eg, glucose-regulated protein 78 (GRP78), that help resolve the ER stress and foster cell survival [1].
  • Mice lacking XBP-1 displayed hypoplastic fetal livers, whose reduced hematopoiesis resulted in death from anemia [3].

Anatomical context of Xbp1


Associations of Xbp1 with chemical compounds


Regulatory relationships of Xbp1


Other interactions of Xbp1


Analytical, diagnostic and therapeutic context of Xbp1

  • 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 [18].
  • To study the function(s) of TREB5 in normal development, we have generated TREB5 deficient mice by gene targeting [19].
  • Southern blot analysis of the mouse genomic DNA demonstrated that positive bands exactly coincide with those expected from sequences of the cloned genes, indicating that the mouse TREB5 gene is present as a single copy [20].
  • 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 [21].
  • Detection of XBP-1 by immunofluorescence at days 0 (control culture without AA and BGP), 8 and 21 showed that the protein has a major cytoplasmic perinuclear location [15].


  1. Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes. Thuerauf, D.J., Marcinko, M., Gude, N., Rubio, M., Sussman, M.A., Glembotski, C.C. Circ. Res. (2006) [Pubmed]
  2. Mouse hepatitis virus infection activates the Ire1/XBP1 pathway of the unfolded protein response. Bechill, J., Chen, Z., Brewer, J.W., Baker, S.C. Adv. Exp. Med. Biol. (2006) [Pubmed]
  3. An essential role in liver development for transcription factor XBP-1. Reimold, A.M., Etkin, A., Clauss, I., Perkins, A., Friend, D.S., Zhang, J., Horton, H.F., Scott, A., Orkin, S.H., Byrne, M.C., Grusby, M.J., Glimcher, L.H. Genes Dev. (2000) [Pubmed]
  4. Activation of hepatitis B virus S promoter by a cell type-restricted IRE1-dependent pathway induced by endoplasmic reticulum stress. Huang, Z.M., Tan, T., Yoshida, H., Mori, K., Ma, Y., Yen, T.S. Mol. Cell. Biol. (2005) [Pubmed]
  5. Human cytomegalovirus protein US11 provokes an unfolded protein response that may facilitate the degradation of class I major histocompatibility complex products. Tirosh, B., Iwakoshi, N.N., Lilley, B.N., Lee, A.H., Glimcher, L.H., Ploegh, H.L. J. Virol. (2005) [Pubmed]
  6. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Calfon, M., Zeng, H., Urano, F., Till, J.H., Hubbard, S.R., Harding, H.P., Clark, S.G., Ron, D. Nature (2002) [Pubmed]
  7. Plasma cell differentiation requires the transcription factor XBP-1. Reimold, A.M., Iwakoshi, N.N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E.M., Friend, D., Grusby, M.J., Alt, F., Glimcher, L.H. Nature (2001) [Pubmed]
  8. Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element. Liou, H.C., Boothby, M.R., Glimcher, L.H. Science (1988) [Pubmed]
  9. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Shaffer, A.L., Shapiro-Shelef, M., Iwakoshi, N.N., Lee, A.H., Qian, S.B., Zhao, H., Yu, X., Yang, L., Tan, B.K., Rosenwald, A., Hurt, E.M., Petroulakis, E., Sonenberg, N., Yewdell, J.W., Calame, K., Glimcher, L.H., Staudt, L.M. Immunity (2004) [Pubmed]
  10. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. Lee, A.H., Chu, G.C., Iwakoshi, N.N., Glimcher, L.H. EMBO J. (2005) [Pubmed]
  11. XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for degradation of glycoproteins in primary B cells. Tirosh, B., Iwakoshi, N.N., Glimcher, L.H., Ploegh, H.L. J. Exp. Med. (2005) [Pubmed]
  12. XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum. Sriburi, R., Jackowski, S., Mori, K., Brewer, J.W. J. Cell Biol. (2004) [Pubmed]
  13. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Tsutsumi, S., Gotoh, T., Tomisato, W., Mima, S., Hoshino, T., Hwang, H.J., Takenaka, H., Tsuchiya, T., Mori, M., Mizushima, T. Cell Death Differ. (2004) [Pubmed]
  14. Rapid turnover of unspliced Xbp-1 as a factor that modulates the unfolded protein response. Tirosh, B., Iwakoshi, N.N., Glimcher, L.H., Ploegh, H.L. J. Biol. Chem. (2006) [Pubmed]
  15. Transcription factor XBP-1 is expressed during osteoblast differentiation and is transcriptionally regulated by parathyroid hormone (PTH). Zambelli, A., Mongiardini, E., Villegas, S.N., Carri, N.G., Boot-Handford, R.P., Wallis, G.A. Cell Biol. Int. (2005) [Pubmed]
  16. The role of brain-derived neurotrophic factor (BDNF)-induced XBP1 splicing during brain development. Hayashi, A., Kasahara, T., Iwamoto, K., Ishiwata, M., Kametani, M., Kakiuchi, C., Furuichi, T., Kato, T. J. Biol. Chem. (2007) [Pubmed]
  17. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Iwakoshi, N.N., Lee, A.H., Vallabhajosyula, P., Otipoby, K.L., Rajewsky, K., Glimcher, L.H. Nat. Immunol. (2003) [Pubmed]
  18. 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. J. Neurochem. (2004) [Pubmed]
  19. Targeted disruption of CRE-binding factor TREB5 gene leads to cellular necrosis in cardiac myocytes at the embryonic stage. Masaki, T., Yoshida, M., Noguchi, S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  20. Isolation and characterization of the gene encoding mouse tax-responsive element-binding protein (TREB) 5. Masaki, T., Noguchi, H., Kobayashi, M., Yoshida, M., Takamatsu, K. DNA Res. (2000) [Pubmed]
  21. Transient cerebral ischemia activates processing of xbp1 messenger RNA indicative of endoplasmic reticulum stress. Paschen, W., Aufenberg, C., Hotop, S., Mengesdorf, T. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
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