XBP1: Wikis

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X-box binding protein 1
Identifiers
Symbols XBP1; TREB5; XBP2
External IDs OMIM194355 MGI98970 HomoloGene3722 GeneCards: XBP1 Gene
RNA expression pattern
PBB GE XBP1 200670 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7494 22433
Ensembl ENSG00000100219 ENSMUSG00000020484
UniProt P17861 O35426
RefSeq (mRNA) NM_001079539 NM_013842
RefSeq (protein) NP_001073007 NP_038870
Location (UCSC) Chr 22:
27.52 - 27.53 Mb
Chr 11:
5.42 - 5.43 Mb
PubMed search [1] [2]

X-box binding protein 1, also known as XBP1, is a protein which in humans is encoded by the XBP1 gene.[1][2] The XBP1 gene is located on chromosome 22 while a closely related pseudogene has been identified and localized to chromosome 5.[3] The XBP1 protein is a transcription factor that regulates the expression of genes important to the proper functioning of the immune system and in the cellular stress response.[4]

Contents

Discovery

The X-box binding protein 1 (XBP-1) is a transcription factor containing a bZIP domain. It was first identified by its ability to bind to the X-box, a conserved transcriptional element in the promoter of the human leukocyte antigen (HLA) DR alpha.[2]

Function

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MHC class II gene regulation

The expression of this protein is required for the transcription of a subset of class II major histocompatibility genes.[5] Furthermore Xbp1 heterodimerizes with other bZIP transcription factors such as c-fos.[5]

Xbp1 expression is controlled by the cytokine IL-4 and the antibody IGHM.[6] Xbp1 in turn controls the expression of IL-6 which promotes plasma cell growth and of immunoglobulins in B lymphocytes.[6]

Plasma cell differentiation

XBP-1 is also essential for differentiation of plasma cells (a type of antibody secreting immune cell).[6] This differentiation requires not only the expression of XBP-1 but the expression of the spliced isoform of XBP-1s. XBP-1 regulates plasma cell differentiation independent of its known functions in the endoplasmic reticulum stress response (see below).[7] Without normal expression of XBP-1, two important plasma cell differentiation-related genes, IRF4 and Blimp1, are misregulated, and XBP-1-lacking plasma cells fail to colonize their long-lived niches in the bone marrow and to sustain antibody secretion.[7]

Viral replication

This protein has also been identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. The generation of XBP-1s during plasma cell differentiation also seems to be the cue for Kaposi's sarcoma-associated herpesvirus and Epstein Barr virus reactivation from latency.

Endoplasmic reticulum stress response

XBP-1 is upregulated as part of the endoplasmic reticulum (ER) stress response, the unfolded protein response (UPR).[6] This increase in transcription requires an ER stress response consensus binding element in the promoter. XBP-1u is ubiquitously expressed but under conditions of ER-stress, the XBP-1u mRNA is processed by IRE1. Activated IRE1 oligomerises and activates its ribonuclease domain through auto (self) phosphorylation. Because the lumen of the ER is continuous with the perinuclear space, the activated ribonuclease domains can penetrate the inner leaflet of the nuclear envelope. Within the nucleus, activated IRE1 catalyses the excision of a 26 nucleotide unconventional intron from XBP-1 mRNA, in a manner mechanistically similar to pre-tRNA splicing. Removal of this intron causes a frame shift in the XBP-1 coding sequence resulting in the translation of a 371 amino acid, 54 kDa, XBP-1s isoform rather than the 261 amino acid, 33 kDa, XBP-1u isoform.

Clinical signficance

A single nucleotide polymorphism, C-116G, in the promoter region of XBP1 has been examined for possible association with personality traits. None was found.[8]

Abnormalities in XBP1 lead to a heightened ER stress and subsequently causes a heightened susceptibility for inflammatory processes.

Specifically in the colon, XBP1 anomalies have been linked to Crohn's disease.[9]

Interactions

XBP1 has been shown to interact with Estrogen receptor alpha.[10]

References

  1. ^ "Entrez Gene: XBP1 X-box binding protein 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7494.  
  2. ^ a b Liou HC, Boothby MR, Finn PW, Davidon R, Nabavi N, Zeleznik-Le NJ, Ting JP, Glimcher LH (March 1990). "A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter". Science (journal) 247 (4950): 1581–4. doi:10.1126/science.2321018. PMID 2321018.  
  3. ^ Liou HC, Eddy R, Shows T, Lisowska-Grospierre B, Griscelli C, Doyle C, Mannhalter J, Eibl M, Glimcher LH (1991). "An HLA-DR alpha promoter DNA-binding protein is expressed ubiquitously and maps to human chromosomes 22 and 5". Immunogenetics 34 (5): 286–92. doi:10.1007/BF00211992. PMID 1718857.  
  4. ^ Yoshida H, Nadanaka S, Sato R, Mori K (2006). "XBP1 is critical to protect cells from endoplasmic reticulum stress: evidence from Site-2 protease-deficient Chinese hamster ovary cells". Cell Structure and Function 31 (2): 117–25. doi:10.1247/csf.06016. PMID 17110785.  
  5. ^ a b Ono SJ, Liou HC, Davidon R, Strominger JL, Glimcher LH (May 1991). "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". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4309–12. doi:10.1073/pnas.88.10.4309. PMID 1903538. PMC 51648. http://www.pnas.org/content/88/10/4309.abstract.  
  6. ^ a b c d Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH (April 2003). "Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1". Nat. Immunol. 4 (4): 321–9. doi:10.1038/ni907. PMID 12612580.  
  7. ^ a b Hu CC, Dougan SK, McGehee AM, Love JC, Ploegh HL (April 2009). "XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells". EMBO J.. doi:10.1038/emboj.2009.117. PMID 19407814.  
  8. ^ Kusumi I, Masui T, Kakiuchi C, Suzuki K, Akimoto T, Hashimoto R, Kunugi H, Kato T, Koyama T (December 2005). "Relationship between XBP1 genotype and personality traits assessed by TCI and NEO-FFI". Neurosci. Lett. 391 (1-2): 7–10. doi:10.1016/j.neulet.2005.08.023. PMID 16154272.  
  9. ^ Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS (September 2008). "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease". Cell 134 (5): 743–56. doi:10.1016/j.cell.2008.07.021. PMID 18775308.  
  10. ^ Ding, Lihua; Yan Jinghua, Zhu Jianhua, Zhong Hongjun, Lu Qiujun, Wang Zonghua, Huang Cuifen, Ye Qinong (Sep. 2003). "Ligand-independent activation of estrogen receptor alpha by XBP-1". Nucleic Acids Res. (England) 31 (18): 5266–74. PMID 12954762.  

Further reading

  • Clarke R, Liu MC, Bouker KB, et al. (2003). "Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling.". Oncogene 22 (47): 7316–39. doi:10.1038/sj.onc.1206937. PMID 14576841.  
  • Nekrutenko A, He J (2007). "Functionality of unspliced XBP1 is required to explain evolution of overlapping reading frames.". Trends Genet. 22 (12): 645–8. doi:10.1016/j.tig.2006.09.012. PMID 17034899.  
  • Liou HC, Eddy R, Shows T, et al. (1991). "An HLA-DR alpha promoter DNA-binding protein is expressed ubiquitously and maps to human chromosomes 22 and 5.". Immunogenetics 34 (5): 286–92. doi:10.1007/BF00211992. PMID 1718857.  
  • Ono SJ, Liou HC, Davidon R, et al. (1991). "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.". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4309–12. doi:10.1073/pnas.88.10.4309. PMID 1903538.  
  • Yoshimura T, Fujisawa J, Yoshida M (1990). "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.". Embo J. 9 (8): 2537–42. PMID 2196176.  
  • Liou HC, Boothby MR, Finn PW, et al. (1990). "A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter.". Science 247 (4950): 1581–4. doi:10.1126/science.2321018. PMID 2321018.  
  • Ponath PD, Fass D, Liou HC, et al. (1993). "The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes.". J. Biol. Chem. 268 (23): 17074–82. PMID 8349596.  
  • Clauss IM, Chu M, Zhao JL, Glimcher LH (1996). "The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core.". Nucleic Acids Res. 24 (10): 1855–64. doi:10.1093/nar/24.10.1855. PMID 8657566.  
  • Kishimoto T, Kokura K, Ohkawa N, et al. (1998). "Enhanced expression of a new class of liver-enriched b-Zip transcription factors, hepatocarcinogenesis-related transcription factor, in hepatocellular carcinomas of rats and humans.". Cell Growth Differ. 9 (4): 337–44. PMID 9563853.  
  • Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22.". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.  
  • Reimold AM, Etkin A, Clauss I, et al. (2000). "An essential role in liver development for transcription factor XBP-1.". Genes Dev. 14 (2): 152–7. PMID 10652269.  
  • Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMID 11076863.  
  • Yoshida H, Matsui T, Yamamoto A, et al. (2002). "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor.". Cell 107 (7): 881–91. doi:10.1016/S0092-8674(01)00611-0. PMID 11779464.  
  • Takahashi S, Suzuki S, Inaguma S, et al. (2002). "Down-regulation of human X-box binding protein 1 (hXBP-1) expression correlates with tumor progression in human prostate cancers.". Prostate 50 (3): 154–61. doi:10.1002/pros.10044. PMID 11813207.  
  • Gu Z, Lee RY, Skaar TC, et al. (2002). "Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780).". Cancer Res. 62 (12): 3428–37. PMID 12067985.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Yoshida H, Matsui T, Hosokawa N, et al. (2003). "A time-dependent phase shift in the mammalian unfolded protein response.". Dev. Cell 4 (2): 265–71. doi:10.1016/S1534-5807(03)00022-4. PMID 12586069.  
  • Shuda M, Kondoh N, Imazeki N, et al. (2004). "Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis.". J. Hepatol. 38 (5): 605–14. doi:10.1016/S0168-8278(03)00029-1. PMID 12713871.  
  • Newman JR, Keating AE (2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays.". Science 300 (5628): 2097–101. doi:10.1126/science.1084648. PMID 12805554.  
  • Kakiuchi C, Iwamoto K, Ishiwata M, et al. (2003). "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder.". Nat. Genet. 35 (2): 171–5. doi:10.1038/ng1235. PMID 12949534.  

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