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 .
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.
There are three main protein sensors that prime ER stress, ATF6, IRE1a
, and PERK.
(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 .
JNK is known to be activated under ER stress via IRE1a
 and caspase-9 is activated under mitochondria-dependent cell death pathway .
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 .
Studies have shown that IRE1a
has a splicing effect on XBP1.