XBP1 

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X-box binding protein 1
Identifiers
Symbols XBP1; TREB5; XBP2
External IDs OMIM: 194355 MGI: 98970 HomoloGene: 3722
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 7494 22433
Ensembl ENSG00000100219 ENSMUSG00000020484
Uniprot P17861 O35426
Refseq NM_001079539 (mRNA)
NP_001073007 (protein)		 NM_013842 (mRNA)
NP_038870 (protein)
Location 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 human gene.12 The XBP1 gene is located on chromosome 22 while a pseudogene has been identified and localized to chromosome 5.3

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

MHC class II gene regulation

The expression of this protein is required for the transcription of a subset of class II major histocompatibility genes.4 Furthermore Xbp1 heterodimerizes with other bZIP transcription factors such as c-fos.4

Xbp1 expression is controlled by the cytokine IL-4 and the antibody IGHM.5 Xbp1 in turn controls the expression of IL-6 which promotes plasma cell growth and of immunoglobulins in B lymphocytes.5

Plasma cell differentiation

XBP-1 is also essential for differentiation of plasma cells (a type of antibody secreting immune cell).5 This differentiation requires not only the expression of XBP-1 but the expression of the spliced isoform of XBP-1s.

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).5 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.6

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.7

References

  1. ^ "Entrez Gene: XBP1 X-box binding protein 1".
  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. PMID 1718857. 
  4. ^ 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. PMID 1903538. PMC: 51648, http://www.pnas.org/content/88/10/4309.abstract. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 

Further reading

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