Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) and upregulates ER molecular chaperones in order to cope with ER stress. UPR is initiated by three ER-localized protein sensors: PERK (PKR-like ER kinase), ATF (activating transcription factor 6), and IRE1 alpha (inositol-requiring enzyme 1 alpha) (1). IRE1 alpha is correlated with X-box binding protein (XBP1) as a potent UPR transcriptional activator (2).

Transcriptional activation of UPR-responsive genes are regulated by the ATF6 and IRE1-XBP1 pathways, which are often regulated by HIFs and contribute to cell survival under ER hypoxic stress (3). UPR signaling can a) inhibit protein translation to restore cell function, b) activate signaling to increase production of molecular chaperones for protein folding, and c) initiate ubiquitination signaling that leads to degradation of misfolded proteins in ER.

IRE1 alpha acts as the sensor of unfolded proteins in the ER. IRE1 alpha not only promotes cell survival but can initiate apoptosis when accumulation of unfolded proteins in the ER causes stress. IRE1 alpha is essential for viability under stress conditions that cause unfolded proteins to accumulate in the ER. IRE1 alpha is a transmembrane protein that has both serine-threonine kinase and endoribonuclease activities and has a theoretical molecular weight of 110 kDa. When detecting phospho-IRE1 alpha, it is recommended to normalize its band intensity with total IRE1 alpha.

References

1. Zheng, W., Xie, W., Yin, D., Luo, R., Liu, M., & Guo, F. (2019). ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell Commun Signal, 17(1), 42. doi:10.1186/s12964-019-0353-3

2. Cho, Y. M., Kim, D. H., Lee, K. H., Jeong, S. W., & Kwon, O. J. (2018). The IRE1alpha-XBP1s pathway promotes insulin-stimulated glucose uptake in adipocytes by increasing PPARgamma activity. Exp Mol Med, 50(8), 102. doi:10.1038/s12276-018-0131-0

3. Xia, Z., Wu, S., Wei, X., Liao, Y., Yi, P., Liu, Y., . . . Liu, J. (2019). Hypoxic ER stress suppresses beta-catenin expression and promotes cooperation between the transcription factors XBP1 and HIF1alpha for cell survival. J Biol Chem, 294(37), 13811-13821. doi:10.1074/jbc.RA119.008353

Long Name

Serine/threonine-protein kinase/endoribonuclease IRE1

Alternate Names

ERN1, hIRE1p, IRE1, Ire1-alpha

Gene Symbol

ERN1

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Product Specific Notices for IRE1 alpha Antibody (142) [Janelia Fluor® 646]

Sold under license from the Howard Hughes Medical Institute, Janelia Research Campus.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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IRE1 alpha Antibody (142) [Janelia Fluor® 646]

Novus Biologicals, part of Bio-Techne | Catalog # NBP2-90017JF646

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Background: IRE1 alpha