Xbp1

Summary

Gene Symbol: Xbp1
Description: X-box binding protein 1
Alias: D11Ertd39e, TREB-5, TREB5, XBP-1, X-box-binding protein 1, tax-responsive element-binding protein 5 homolog
Species: mouse
Products:     Xbp1

Top Publications

  1. Acosta Alvear D, Zhou Y, Blais A, Tsikitis M, Lents N, Arias C, et al. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell. 2007;27:53-66 pubmed
    Using genome-wide approaches, we have elucidated the regulatory circuitry governed by the XBP1 transcription factor, a key effector of the mammalian unfolded protein response (UPR), in skeletal muscle and secretory cells...
  2. Masaki T, Yoshida M, Noguchi S. Targeted disruption of CRE-binding factor TREB5 gene leads to cellular necrosis in cardiac myocytes at the embryonic stage. Biochem Biophys Res Commun. 1999;261:350-6 pubmed
    b>TREB5 (hXBP-1) is a basic region leucine zipper protein which binds to a CRE-like element in both human T-cell leukemia virus type 1 and MHC class II genes...
  3. Yamamoto K, Sato T, Matsui T, Sato M, Okada T, Yoshida H, et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell. 2007;13:365-76 pubmed
    ..is solely responsible for transcriptional induction of ER chaperones and that ATF6alpha heterodimerizes with XBP1 for the induction of ER-associated degradation components. ATF6alpha(-/-) MEFs are sensitive to ER stress...
  4. Ozcan L, Ergin A, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9:35-51 pubmed publisher
    ..Taken together, our results may provide the basis for a novel treatment of obesity...
  5. Benhamron S, Hadar R, Iwawaky T, So J, Lee A, Tirosh B. Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells. Eur J Immunol. 2014;44:867-76 pubmed publisher
    Inositol-requiring enzyme 1 (IRE1) is a kinase and ribonuclease that executes the splicing of X box binding protein 1 (XBP-1) mRNA in response to the accumulation of unfolded protein in the ER, a signal cascade termed the unfolded ..
  6. Zeng L, Xiao Q, Chen M, Margariti A, Martin D, Ivetic A, et al. Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis. Circulation. 2013;127:1712-22 pubmed publisher
    ..The X-box binding protein 1 (XBP1) is believed to be a signal transducer in the endoplasmic reticulum stress response...
  7. Ozcan U, Cao Q, Yilmaz E, Lee A, Iwakoshi N, Ozdelen E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306:457-61 pubmed
    ..Pharmacologic manipulation of this pathway may offer novel opportunities for treating these common diseases. ..
  8. Lisbona F, Rojas Rivera D, Thielen P, Zamorano S, Todd D, Martinon F, et al. BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha. Mol Cell. 2009;33:679-91 pubmed publisher
    ..Our results suggest a role for BI-1 in early adaptive responses against ER stress that contrasts with its known downstream function in apoptosis. ..
  9. Majumder M, Huang C, Snider M, Komar A, Tanaka J, Kaufman R, et al. A novel feedback loop regulates the response to endoplasmic reticulum stress via the cooperation of cytoplasmic splicing and mRNA translation. Mol Cell Biol. 2012;32:992-1003 pubmed publisher
    ..which initiates cytoplasmic splicing of the mRNA encoding the transcription factor X-box binding protein 1 (XBP1). XBP1 induces transcription of genes involved in protein quality control...

More Information

Publications62

  1. Jurczak M, Lee A, Jornayvaz F, Lee H, Birkenfeld A, Guigni B, et al. Dissociation of inositol-requiring enzyme (IRE1?)-mediated c-Jun N-terminal kinase activation from hepatic insulin resistance in conditional X-box-binding protein-1 (XBP1) knock-out mice. J Biol Chem. 2012;287:2558-67 pubmed publisher
    ..The ER stress response protein, X-box-binding protein-1 (XBP1), was recently shown to regulate hepatic lipogenesis, suggesting that hepatic insulin resistance in models of ER ..
  2. Zhou Y, Lee J, Reno C, Sun C, Park S, Chung J, et al. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nat Med. 2011;17:356-65 pubmed publisher
  3. Hetz C, Lee A, Gonzalez Romero D, Thielen P, Castilla J, Soto C, et al. Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis. Proc Natl Acad Sci U S A. 2008;105:757-62 pubmed publisher
  4. Chen H, Qi L. SUMO modification regulates the transcriptional activity of XBP1. Biochem J. 2010;429:95-102 pubmed publisher
    ..b>XBP1 (X-box-binding protein 1), a key transcription factor of the UPR, is critical in maintaining ER homoeostasis...
  5. Lee A, Scapa E, Cohen D, Glimcher L. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science. 2008;320:1492-6 pubmed publisher
    ..We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid ..
  6. Lee A, Iwakoshi N, Glimcher L. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003;23:7448-59 pubmed
    ..Further, our observations suggest the existence of additional, as-yet-unknown, key regulators of the UPR. ..
  7. Zeng L, Zampetaki A, Margariti A, Pepe A, Alam S, Martin D, et al. Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. Proc Natl Acad Sci U S A. 2009;106:8326-31 pubmed publisher
    X-box binding protein 1 (XBP1) is a key signal transducer in endoplasmic reticulum stress response, and its potential role in the atherosclerosis development is unknown...
  8. Lee J, Sun C, Zhou Y, Lee J, Gokalp D, Herrema H, et al. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med. 2011;17:1251-60 pubmed publisher
  9. Lee A, Chu G, Iwakoshi N, Glimcher L. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J. 2005;24:4368-80 pubmed
    ..These data lead us to propose that XBP-1 is both necessary and sufficient for the full biogenesis of the secretory machinery in exocrine cells...
  10. Clauss I, Gravallese E, Darling J, Shapiro F, Glimcher M, Glimcher L. In situ hybridization studies suggest a role for the basic region-leucine zipper protein hXBP-1 in exocrine gland and skeletal development during mouse embryogenesis. Dev Dyn. 1993;197:146-56 pubmed
    ..It is intriguing that the promoter regions of several such genes contain potential hXBP-1 binding sites. ..
  11. Sriburi R, Bommiasamy H, Buldak G, Robbins G, Frank M, Jackowski S, et al. Coordinate regulation of phospholipid biosynthesis and secretory pathway gene expression in XBP-1(S)-induced endoplasmic reticulum biogenesis. J Biol Chem. 2007;282:7024-34 pubmed
    ..We propose that XBP-1(S) regulates ER abundance by coordinately increasing the supply of membrane phospholipids and ER proteins, the key ingredients for ER biogenesis. ..
  12. Wang F, Chen Y, Ouyang H. Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation. Biochem J. 2011;433:245-52 pubmed publisher
    b>XBP1 (X-box-binding protein 1) is a key modulator of the UPR (unfolded protein response), which is involved in a wide range of pathological and physiological processes...
  13. Tirosh B, Iwakoshi N, Glimcher L, Ploegh H. Rapid turnover of unspliced Xbp-1 as a factor that modulates the unfolded protein response. J Biol Chem. 2006;281:5852-60 pubmed
    ..We suggest that the degradation of Xbp-1u is required to prevent uncontrolled activation of the UPR while allowing short dwell times for initiation of this response. ..
  14. Wang S, Chen Z, Lam V, Han J, Hassler J, Finck B, et al. IRE1?-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis. Cell Metab. 2012;16:473-86 pubmed publisher
    ..we identify an essential role for the inositol-requiring transmembrane kinase/endoribonuclease 1? (IRE1?)-X box binding protein 1 (XBP1) arm of the UPR in regulation of hepatic very low-density lipoprotein (VLDL) assembly and secretion...
  15. Adolph T, Tomczak M, Niederreiter L, Ko H, Böck J, Martínez Naves E, et al. Paneth cells as a site of origin for intestinal inflammation. Nature. 2013;503:272-6 pubmed publisher
    ..Deletion of the unfolded protein response (UPR) transcription factor X-box binding protein-1 (Xbp1) in intestinal epithelial cells, the human orthologue of which harbours rare inflammatory bowel disease risk ..
  16. Sha H, He Y, Chen H, Wang C, Zenno A, Shi H, et al. The IRE1alpha-XBP1 pathway of the unfolded protein response is required for adipogenesis. Cell Metab. 2009;9:556-64 pubmed publisher
    ..Here we demonstrate that the IRE1alpha-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis...
  17. Liu Y, Adachi M, Zhao S, Hareyama M, Koong A, Luo D, et al. Preventing oxidative stress: a new role for XBP1. Cell Death Differ. 2009;16:847-57 pubmed publisher
    ..We have investigated the contribution of X-box-binding protein (XBP1), a major endoplasmic reticulum stress-linked transcriptional factor, to cellular resistance to oxidative stress...
  18. Martinon F, Chen X, Lee A, Glimcher L. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol. 2010;11:411-8 pubmed publisher
    ..the endoplasmic reticulum (ER) stress sensor kinase IRE1alpha and its downstream target, the transcription factor XBP1. Previously described ER-stress target genes of XBP1 were not induced by TLR signaling...
  19. Iwakoshi N, Pypaert M, Glimcher L. The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J Exp Med. 2007;204:2267-75 pubmed
    ..Overexpression of XBP-1 in hematopoietic progenitors rescued and enhanced DC development. Remarkably, in contrast to other cell types we have examined, the XBP-1 pathway was constitutively activated in immature DCs. ..
  20. Kaser A, Lee A, Franke A, Glickman J, Zeissig S, Tilg H, et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell. 2008;134:743-56 pubmed publisher
    ..The transcription factor XBP1, a key component of the endoplasmic reticulum (ER) stress response, is required for development and maintenance of ..
  21. Lee A, Heidtman K, Hotamisligil G, Glimcher L. Dual and opposing roles of the unfolded protein response regulated by IRE1alpha and XBP1 in proinsulin processing and insulin secretion. Proc Natl Acad Sci U S A. 2011;108:8885-90 pubmed publisher
    As a key regulator of the unfolded protein response, the transcription factor XBP1 activates genes in protein secretory pathways and is required for the development of certain secretory cells...
  22. Iwakoshi N, Lee A, Vallabhajosyula P, Otipoby K, Rajewsky K, Glimcher L. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol. 2003;4:321-9 pubmed
    ..Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR. ..
  23. Hetz C, Thielen P, Matus S, Nassif M, Court F, Kiffin R, et al. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev. 2009;23:2294-306 pubmed publisher
    ..Our results reveal a new function of XBP-1 in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration. ..
  24. Zeng L, Liu Y, Sha H, Chen H, Qi L, Smith J. XBP-1 couples endoplasmic reticulum stress to augmented IFN-beta induction via a cis-acting enhancer in macrophages. J Immunol. 2010;185:2324-30 pubmed publisher
    ..Our findings have broader mechanistic implications for the pathogenesis of diseases involving ER stress and type I IFN, including viral infection, ischemia-reperfusion injury, protein misfolding, and inflammatory diseases. ..
  25. Calfon M, Zeng H, Urano F, Till J, Hubbard S, Harding H, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002;415:92-6 pubmed
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes. ..
  26. Vald s P, Mercado G, Vidal R, Molina C, Parsons G, Court F, et al. Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1. Proc Natl Acad Sci U S A. 2014;111:6804-9 pubmed publisher
    ..Here we report that developmental ablation of X-Box binding protein 1 (XBP1) in the nervous system, a key regulator of the unfolded protein response (UPR), protects dopaminergic neurons ..
  27. Vidal R, Figueroa A, Court F, Thielen P, Molina C, Wirth C, et al. Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy. Hum Mol Genet. 2012;21:2245-62 pubmed publisher
    ..the functional contribution of ER stress to HD by targeting the expression of two main UPR transcription factors, XBP1 and ATF4 (activating transcription factor 4), in full-length mutant Huntingtin (mHtt) transgenic mice...
  28. Hur K, So J, Ruda V, Frank Kamenetsky M, Fitzgerald K, Koteliansky V, et al. IRE1? activation protects mice against acetaminophen-induced hepatotoxicity. J Exp Med. 2012;209:307-18 pubmed publisher
    ..unfolded protein, or endoplasmic reticulum (ER), stress response by activating its downstream transcription factor XBP1 via an unconventional splicing mechanism...
  29. Hu F, Yu X, Wang H, Zuo D, Guo C, Yi H, et al. ER stress and its regulator X-box-binding protein-1 enhance polyIC-induced innate immune response in dendritic cells. Eur J Immunol. 2011;41:1086-97 pubmed publisher
    ..Our findings suggest that evolutionarily conserved ER stress response and XBP-1 may function collaboratively with innate immunity to maintain cellular homeostasis. ..
  30. So J, Hur K, Tarrio M, Ruda V, Frank Kamenetsky M, Fitzgerald K, et al. Silencing of lipid metabolism genes through IRE1?-mediated mRNA decay lowers plasma lipids in mice. Cell Metab. 2012;16:487-99 pubmed publisher
    b>XBP1 is a key regulator of the unfolded protein response (UPR), which is involved in a wide range of physiological and pathological processes...
  31. Rutkowski D, Arnold S, Miller C, Wu J, Li J, Gunnison K, et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol. 2006;4:e374 pubmed
    ..It underscores the contribution of posttranscriptional and posttranslational mechanisms in influencing this outcome. ..
  32. Iwawaki T, Akai R, Yamanaka S, Kohno K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci U S A. 2009;106:16657-62 pubmed publisher
    ..These findings reveal that IRE1alpha plays an essential function in extraembryonic tissues and highlight the relationship of physiological ER stress and angiogenesis in the placenta during pregnancy in mammals. ..
  33. Huh W, Esen E, Geahlen J, Bredemeyer A, Lee A, Shi G, et al. XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum. Gastroenterology. 2010;139:2038-49 pubmed publisher
    ..The transcription factor MIST1 is required for granulogenesis of ZCs. The transcription factor XBP1 binds the Mist1 promoter and induces its expression in vitro and expands the ER in other cell types...
  34. Todd D, McHeyzer Williams L, Kowal C, Lee A, Volpe B, Diamond B, et al. XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development. J Exp Med. 2009;206:2151-9 pubmed publisher
    ..b>X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development ..
  35. Li J, Wang J, Zhang S. Preconditioning with endoplasmic reticulum stress mitigates retinal endothelial inflammation via activation of X-box binding protein 1. J Biol Chem. 2011;286:4912-21 pubmed publisher
    ..In the present study, we investigated the role of X-box binding protein 1 (XBP1) in retinal adhesion molecule expression, leukostasis, and vascular leakage...
  36. Tirosh B, Iwakoshi N, Glimcher L, Ploegh H. XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for degradation of glycoproteins in primary B cells. J Exp Med. 2005;202:505-16 pubmed
    ..We conclude that in primary B cells, the XBP-1 pathway promotes synthesis and secretion of IgM, but does not seem to be involved in the degradation of ER proteins, including that of mu chains themselves. ..
  37. Akiyama M, Liew C, Lu S, Hu J, Martinez R, Hambro B, et al. X-box binding protein 1 is essential for insulin regulation of pancreatic ?-cell function. Diabetes. 2013;62:2439-49 pubmed publisher
    ..X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR), and its deficiency in ?..
  38. Goldfinger M, Laviad E, Hadar R, Shmuel M, Dagan A, Park H, et al. De novo ceramide synthesis is required for N-linked glycosylation in plasma cells. J Immunol. 2009;182:7038-47 pubmed publisher
    ..Our results underscore ceramide biosynthesis as a key metabolic pathway in the process of PC differentiation and reveal a previously unknown functional link between sphingolipids and N-linked glycosylation in PCs. ..
  39. Hu C, Dougan S, McGehee A, Love J, Ploegh H. XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO J. 2009;28:1624-36 pubmed publisher
    ..They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies. ..
  40. Shaffer A, Shapiro Shelef M, Iwakoshi N, Lee A, Qian S, Zhao H, et al. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity. 2004;21:81-93 pubmed
    ..of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation ..
  41. Cho Y, Kim D, Kwak S, Jeong S, Kwon O. X-box binding protein 1 enhances adipogenic differentiation of 3T3-L1 cells through the downregulation of Wnt10b expression. FEBS Lett. 2013;587:1644-9 pubmed publisher
    ..Recently, the pro-adipogenic function of XBP1, a transcription factor upregulated by endoplasmic reticulum stress, has been reported...
  42. Deng Y, Wang Z, Tao C, Gao N, Holland W, Ferdous A, et al. The Xbp1s/GalE axis links ER stress to postprandial hepatic metabolism. J Clin Invest. 2013;123:455-68 pubmed publisher
    ..Our results provide evidence that the Xbp1s/GalE pathway functions as a novel regulatory nexus connecting the UPR to the characteristic postprandial metabolic changes in hepatocytes. ..
  43. Reimold A, Etkin A, Clauss I, Perkins A, Friend D, Zhang J, et al. An essential role in liver development for transcription factor XBP-1. Genes Dev. 2000;14:152-7 pubmed
    ..Therefore, XBP-1 is a transcription factor essential for hepatocyte growth. ..
  44. Margariti A, Li H, Chen T, Martin D, Vizcay Barrena G, Alam S, et al. XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation. J Biol Chem. 2013;288:859-72 pubmed publisher
    Sustained activation of X-box-binding protein 1 (XBP1) results in endothelial cell (EC) apoptosis and atherosclerosis development...
  45. Iwawaki T, Akai R, Kohno K, Miura M. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med. 2004;10:98-102 pubmed
    ..We used transgenic animals expressing the ER stress indicator to show that it can be used to monitor physiological and pathological ER stress in vivo. ..
  46. Love K, Mahon K, Levins C, Whitehead K, Querbes W, Dorkin J, et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci U S A. 2010;107:1864-9 pubmed publisher
    ..03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system. ..
  47. Hao L, Vassena R, Wu G, Han Z, Cheng Y, Latham K, et al. The unfolded protein response contributes to preimplantation mouse embryo death in the DDK syndrome. Biol Reprod. 2009;80:944-53 pubmed publisher
    ..Our results indicate that the unfolded protein response is induced in embryos destined to die of DDK syndrome and that the embryonic death observed is associated with inability to resolve the associated ER stress. ..
  48. Sriburi R, Jackowski S, Mori K, Brewer J. XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum. J Cell Biol. 2004;167:35-41 pubmed
    ..Here, we report that enforced expression of XBP1(S), the active form of the XBP1 transcription factor generated by UPR-mediated splicing of XBP1 mRNA, is sufficient ..
  49. Luo S, Mao C, Lee B, Lee A. GRP78/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development. Mol Cell Biol. 2006;26:5688-97 pubmed
    ..These findings provide the first evidence that GRP78 is essential for embryonic cell growth and pluripotent cell survival. ..
  50. Park S, Zhou Y, Lee J, Lu A, Sun C, Chung J, et al. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med. 2010;16:429-37 pubmed publisher
    ..Our results define a previously unknown insulin receptor signaling pathway and provide new mechanistic insight into the development of ER stress during obesity. ..
  51. Novosyadlyy R, Kurshan N, Lann D, Vijayakumar A, Yakar S, LeRoith D. Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum. Cell Death Differ. 2008;15:1304-17 pubmed publisher
  52. Kanemoto S, Kondo S, Ogata M, Murakami T, Urano F, Imaizumi K. XBP1 activates the transcription of its target genes via an ACGT core sequence under ER stress. Biochem Biophys Res Commun. 2005;331:1146-53 pubmed
    ..protein kinase/endoribonuclease IRE1 is activated by endoplasmic reticulum stress and subsequently processes XBP1 mRNA to generate an active form of XBP1 protein...
  53. Cameron T, Gresshoff I, Bell K, Piróg K, Sampurno L, Hartley C, et al. Cartilage-specific ablation of XBP1 signaling in mouse results in a chondrodysplasia characterized by reduced chondrocyte proliferation and delayed cartilage maturation and mineralization. Osteoarthritis Cartilage. 2015;23:661-70 pubmed publisher
    To investigate the in vivo role of the IRE1/XBP1 unfolded protein response (UPR) signaling pathway in cartilage. Xbp1(flox/flox)...