ERN1

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ERN1

A gene on chromosome 17q24.2 that encodes the ubiquitously expressed endoplasmic reticulum (ER)-to-nucleus signalling 1 protein, which has intrinsic kinase and endoribonuclease activities and plays a key role in altering gene expression in response to endoplasmic reticulum-based stress signals. ERN1 senses unfolded proteins in the ER lumen, leading to enzyme auto-activation; the active endoribonuclease domain splices XBP1 mRNA, generating a new C-terminus and converting it into a potent unfolded-protein response transcriptional activator, triggering growth arrest and apoptosis.
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The metabolic ER stress sensor IRE1a suppresses alternative activation of macrophages and impairs energy expenditure in obesity.
A recent study showed that the ER luminal cochaperone ERdj4/ DNAJB9 is required for the complex formation between BiP and the luminal domain of IRE1a, thereby maintaining IRE1a in a monomeric, inactive state in the absence of ER stress [4].
Wood et al., "ER stress signalling through eIF2a and CHOP, but not IRE1a, attenuates adipogenesis in mice," Diabetologia, vol.
erinaceus mycelia were associated with the inhibition on the endoplasmic reticulum stress by lowering the expression of Fas and Bax via inositol-requiring enzyme 1a (IRE1a)/tumor necrosis factor receptor-associated factor 2 (TRAF2) complex formation and phosphorylation of c-Jun N-terminal protein kinase (JNK) 1/2, p38 and nuclear factor kappa light chain enhancer of activated B cell (NF-[kappa]B) pathways.
Lisbona et al., "BAX inhibitor-1 regulates autophagy by controlling the IRE1a branch of the unfolded protein response," The EMBO Journal, vol.
(76) One of these ER receptors, IRE1a, accounts for the pro-inflammatory potential of the UPR by recruiting TRAF2 to the ER membrane and thus the activation of NF-[kappa]B and the production of IL-6.
Nonetheless, in two preclinical models of cancer cachexia, the activation of several markers of ER stress (e.g., IRE1a, XBP-1, and ATF6) was accompanied by the suppression of mTORC1 signaling, activation of protein breakdown, and dysregulated AMPK activation [113].
JNK is known to be activated under ER stress via IRE1a [17] and caspase-9 is activated under mitochondria-dependent cell death pathway [15].
ELUCIDATING THE ROLE OF THE PRO-SURVIVAL TO PRO-DEATH MOLECULAR SWITCH IN THE IRE1A SIGNALING PATHWAY IN ARABIDOPSIS THALIANA.
Glucose-regulated protein 78 (GRP78), also called immunoglobulin heavy chain binding protein (BIP), is a molecular chaperone of ER stress sensor PKR-like ER kinase (PERK), inositol-requiring enzyme-1A (IRE1A), and activating transcription factor-6 (ATF6) and is often used as a parameter to evaluate ER stress [24].
Studies have shown that IRE1a has a splicing effect on XBP1.