Abstract
IRE1α (inositol-requiring enzyme 1 alpha, referred to IRE1 hereafter) is an Endoplasmic Reticulum (ER) resident transmembrane enzyme with cytosolic kinase/RNAse activities. Upon ER stress IRE1 is activated through trans-autophosphorylation and oligomerization, resulting in a conformational change of the RNase domain, thereby promoting two signaling pathways: i) the non-conventional splicing of XBP1 mRNA and ii) the regulated IRE1-dependent decay of RNA (RIDD). IRE1 RNase activity has been linked to diverse pathologies such as cancer or inflammatory, metabolic, and degenerative diseases and the modulation of IRE1 activity is emerging as an appealing therapeutic strategy against these diseases. Several modulators of IRE1 activity have been reported in the past, but none have successfully translated into the clinics as yet. Based on our expertise in the field, we describe in this chapter the approaches and protocols we used to discover novel IRE1 modulators and characterize their effect on IRE1 activity.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
