Disease relevance of Ern1

• Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis [1].
• Our results indicate that genetically modified mice such as transgenic mice with a dominant-negative form of Ire1 alpha might provide further understanding of the pathogenic mechanisms of Alzheimer's disease and other neurodegenerative disorders [2].
• Morphological and biochemical studies using a dominant-negative form of mouse Ire1 alpha have revealed that cell death caused by ER stress can be attributed to apoptosis, and that the downregulation of the UPR enhances the apoptotic process in the mouse neuroblastoma cell line, Neuro2a [2].
• Mouse hepatitis virus infection activates the Ire1/XBP1 pathway of the unfolded protein response [3].
• In this report, we have examined the role of IRE1-alpha and XBP1 in activation of the hepatitis B virus S promoter by ER stress [4].

High impact information on Ern1

• In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR) [5].
• Three ER transmembrane protein kinases (Ire1alpha, Ire1beta, and PERK) have been implicated as proximal effectors of the mammalian UPR [6].
• Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1 [1].
• The mammalian unfolded protein response (UPR) includes two major branches: one(s) specific to ER stress (Ire1/XBP-1 and ATF6-dependent), and one(s) shared by other cellular stresses (PERK/eIF-2alpha phosphorylation-dependent) [7].
• PERK and Ire1alpha and eIF2alpha are also activated in calreticulin-deficient cells [8].

Biological context of Ern1

• In yeast, an endoplasmic reticulum (ER)-associated protein, Ire1p, is believed to initiate the unfolded protein response (UPR), that is responsible for protein folding in the ER under stressed conditions [2].
• We have previously reported that familial Alzheimer's disease linked presenilin-1 variants downregulate the signaling pathway of the UPR by affecting the phosphorylation of Ire1 alpha [2].

Anatomical context of Ern1

• Characterization of mouse Ire1 alpha: cloning, mRNA localization in the brain and functional analysis in a neural cell line [2].

Analytical, diagnostic and therapeutic context of Ern1

• In contrast, FAD-linked PS1 mutants were confirmed to disturb UPR signaling by inhibiting activation of both Ire1alpha and ATF6, both of which are endoplasmic reticulum (ER) stress transducers in the UPR [9].

References