X-Box Binding Protein 1 (XBP1)

TREB5; XBP2; Tax-responsive element-binding protein 5

SPN	U246
HGNC	12801
MGI	98970
PubMed	9343412
RGD	1303073
UniProt	P17861
Wiki	XBP1

X-box binding protein 1is a a transcription factor that regulates MHC class II genes by binding to a promoter element referred to as an X box. This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. It may increase expression of viral proteins by acting as the DNA binding partner of a viral transactivator. It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). The resulting loss of 26 nt from the spliced mRNA causes a frame-shift and an isoform XBP1(S), which is the functionally active transcription factor.

Reference

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Science 247:1581-1584(1990) [PubMed] [Europe PMC] [Abstract]

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EMBO J. 9:2537-2542(1990) [PubMed] [Europe PMC] [Abstract]

"The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes."
J. Biol. Chem. 268:17074-17082(1993) [PubMed] [Europe PMC] [Abstract]

"XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor."
Cell 107:881-891(2001) [PubMed] [Europe PMC] [Abstract]

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Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"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."
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"Transcription factor B cell lineage-specific activator protein regulates the gene for human X-box binding protein 1."
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"The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core."
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"Plasma cell differentiation requires the transcription factor XBP-1."
Nature 412:300-307(2001) [PubMed] [Europe PMC] [Abstract]

"Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder."
Nat. Genet. 35:171-175(2003) [PubMed] [Europe PMC] [Abstract]

"XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum."
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"XBP1 is critical to protect cells from endoplasmic reticulum stress: evidence from Site-2 protease-deficient Chinese hamster ovary cells."
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"pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response activator pXBP1(S) in mammalian ER stress response."
J. Cell Biol. 172:565-575(2006) [PubMed] [Europe PMC] [Abstract]

"Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1."
Dev. Cell 13:365-376(2007) [PubMed] [Europe PMC] [Abstract]

"Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the mammalian unfolded protein response."
J. Cell Sci. 122:2877-2886(2009) [PubMed] [Europe PMC] [Abstract]

"Cotranslational targeting of XBP1 protein to the membrane promotes cytoplasmic splicing of its own mRNA."
Mol. Cell 34:191-200(2009) [PubMed] [Europe PMC] [Abstract]

"Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow."
Proc. Natl. Acad. Sci. U.S.A. 106:8326-8331(2009) [PubMed] [Europe PMC] [Abstract]

"A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response."
Nat. Med. 16:438-445(2010) [PubMed] [Europe PMC] [Abstract]

"Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation."
Biochem. J. 433:245-252(2011) [PubMed] [Europe PMC] [Abstract]

"Translational pausing ensures membrane targeting and cytoplasmic splicing of XBP1u mRNA."
Science 331:586-589(2011) [PubMed] [Europe PMC] [Abstract]

"Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis."
Circulation 127:1712-1722(2013) [PubMed] [Europe PMC] [Abstract]

"XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation."
J. Biol. Chem. 288:859-872(2013) [PubMed] [Europe PMC] [Abstract]

"XBP1 induces snail expression to promote epithelial-to-mesenchymal transition and invasion of breast cancer cells."
Cell. Signal. 27:82-89(2015) [PubMed] [Europe PMC] [Abstract]

"Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u."
EMBO J. 33:2492-2506(2014) [PubMed] [Europe PMC] [Abstract]

"Unspliced X-box-binding protein 1 (XBP1) protects endothelial cells from oxidative stress through interaction with histone deacetylase 3."
J. Biol. Chem. 289:30625-30634(2014) [PubMed] [Europe PMC] [Abstract]

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