XBP1
XBP1 (X-box binding protein 1, also known as XBP2) is a basic leucine zipper transcription factor that drives the unfolded protein response during endoplasmic reticulum stress. It also regulates MHC class II genes and contributes to plasma cell differentiation, lipid metabolism and tumour progression. Browse Assay Genie's current range of XBP1 research reagents below, or read on for the biology behind the target.
XBP1 acts as a stress-inducible transcriptional activator when unfolded proteins accumulate in the endoplasmic reticulum (ER). It binds the unfolded protein response element (UPRE) and the ER stress response element (ERSE) to induce genes for ER chaperones and ER-associated degradation (ERAD) components. This increases the folding and degradation capacity of the ER and helps maintain ER homeostasis. XBP1 also induces phospholipid biosynthesis and ER expansion, and supports immunoglobulin and interleukin-6 production during plasma cell differentiation.
The XBP1 gene belongs to the basic leucine zipper (bZIP) group of proteins. Its activity depends on an unconventional splicing event. Under ER stress, the endonuclease IRE1 removes 26 nucleotides from the mRNA. This causes a frame-shift and produces the active isoform XBP1(S). The unspliced isoform, XBP1(U), is constitutively expressed and is thought to act as a negative feedback regulator of XBP1(S), shutting off target gene transcription during recovery from ER stress. XBP1 is found in the endoplasmic reticulum, nucleus and cytoplasm. A pseudogene has been identified on chromosome 5.
XBP1 was first described as a factor that binds the X box promoter element to regulate MHC class II genes. It also binds an enhancer in the T cell leukaemia virus type 1 promoter. Beyond the unfolded protein response, it has roles in endothelial cell growth, angiogenesis and autophagy, adipocyte differentiation, hepatic lipogenesis and glucose homeostasis. It promotes survival of dopaminergic neurons and myeloma cells. It acts as an oncogene in breast cancer by stimulating SNAI1 transcription to drive epithelial-to-mesenchymal transition, migration and invasion. It also lowers blood glucose by binding FOXO1 and promoting its proteasomal degradation.
XBP1 induces ER chaperones and ERAD components, making it a central readout of IRE1 signalling and ER stress adaptation.
XBP1 supports myeloma cell survival and promotes breast cancer EMT, migration and invasion through SNAI1 transcription.
XBP1 improves insulin sensitivity and glucose tolerance, regulates lipogenic genes in hepatocytes and promotes FOXO1 degradation.
XBP1 contributes to immunoglobulin and interleukin-6 production during plasma cell differentiation and regulates MHC class II genes.
XBP1 is a transcription factor that activates unfolded protein response genes during ER stress, including ER chaperones and ERAD components. It also induces phospholipid biosynthesis and ER expansion, and contributes to plasma cell differentiation, endothelial cell proliferation and metabolic regulation in the liver.
XBP2 is an alias of XBP1. XBP1(S) is the active transcription factor, produced when IRE1 splices out 26 nucleotides from the mRNA during ER stress. XBP1(U), from the unspliced mRNA, is constitutively expressed and thought to act as a negative feedback regulator of XBP1(S).
Mouse and rat both have an Xbp1 ortholog. The UniProt annotation links XBP1 to tumour progression in breast cancer, myeloma cell survival, atherosclerosis development and dopaminergic neuron survival. Check the datasheet of any product for its validated reactivity.
Other ER stress pathway components, transcription factors and signalling partners linked to XBP1 function.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P17861; product specifications from Assay Genie datasheets.