Background: The mammalian endoplasmic reticulum (ER) continuously adapts to the cellular secretory load by the activation of an unfolded protein response (UPR). This stress response results in expansion of the ER, upregulation of proteins involved in protein folding and degradation, and attenuation of protein synthesis. The response is orchestrated by three signalling pathways each activated by a specific signal transducer, either inositol requiring enzyme α (IRE1α), double-stranded RNA-activated protein kinase-like ER kinase (PERK) or activating transcription factor 6 (ATF6). Activation of IRE1α results in its oligomerisation, autophosphorylation and stimulation of its ribonuclease activity. The ribonuclease initiates the splicing of an intron from mRNA encoding the transcription factor, X-box binding protein 1 (XBP1), as well as degradation of specific mRNAs and microRNAs. Methods: To investigate the consequence of expression of exogenous XBP1, we generated a stable cell-line expressing spliced XBP1 mRNA under the control of an inducible promotor. Results: Following induction of expression, high levels of XBP1 protein were detected, which allowed upregulation of target genes in the absence of induction of the UPR. Remarkably under stress conditions, the expression of exogenous XBP1 repressed splicing of endogenous XBP1 mRNA without repressing the activation of PERK. Conclusions: These results illustrate that a feedback mechanism exists to attenuate Ire1α ribonuclease activity in the presence of XBP1.
Pubmed ID: 29062910 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A commercial antibody supplier and provider of various services.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsThis unknown targets Xbp-1 (COOH terminus)
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets Actin N-terminal antibody produced in rabbit
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets PERK (C33E10) Rabbit mAb
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsCommercially available software for visualization and analysis of next generation sequencing data. Used for viewing, exploring, and sharing of NGS analysis results. Complete toolkit for genomics, transcriptomics, epigenomics, and metagenomics in one program.
View all literature mentions