IPA, a potent second-generation IRE1 activator of low molecular weight, activates the RNase domain via interaction with ATP-binding site, which in turn predisposes the kinase domain to oligomerize.

2015年5月19日 · We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile.

2020年12月14日 · The RNase activity of Inositol-Requiring Enzyme 1 (IRE1) can be allosterically regulated by ATP-competitive inhibitors of the IRE1 kinase domain.

2024年5月7日 · Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to...

potent small molecule, IPA, that binds to IRE1’s ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile.

2015年5月19日 · We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile.

2024年4月1日 · IRE1 is an ER-resident type 1 transmembrane protein that comprises both BiP-binding (binding-immunoglobulin protein) and misfolded protein binding domain in the ER lumen as well as kinase and endoribonuclease catalytic domains in the cytosol.

2024年6月1日 · NF-κB and XBP1 signaling was in turn activated by the endoplasmic reticulum (ER)-stress sensor inositol-requiring enzyme 1 (IRE1), which mediates the unfolded protein response. Co-treatment with an inhibitor of IRE1 kinase and RNase activities, decreased phospho-NF-κB and XBP1s expression and the production of pro-inflammatory mediators.

In the endoplasmic reticulum, unfolded proteins stimulate Ire1 autophosphorylation and RNase activity. The crystal structure of the dephosphorylated kinase/RNase domain of human Ire1 bound to ADP provides insight into the autophosphorylation ...

2021年2月5日 · Inositol-requiring enzyme type 1 (IRE1) is a serine/threonine kinase acting as one of three branches of the Unfolded Protein Response (UPR) signaling pathway, which is activated upon endoplasmic reticulum (ER) stress conditions. It is known to be capable of inducing both pro-survival and pro-apoptot …