Ontology highlight
ABSTRACT:
SUBMITTER: Mendez AS
PROVIDER: S-EPMC4436593 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Mendez Aaron S AS Alfaro Jennifer J Morales-Soto Marisol A MA Dar Arvin C AC McCullagh Emma E Gotthardt Katja K Li Han H Acosta-Alvear Diego D Sidrauski Carmela C Korennykh Alexei V AV Bernales Sebastian S Shokat Kevan M KM Walter Peter P
eLife 20150519
Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. 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, r ...[more]