2019年11月6日 · Here, by reconstituting components of human UPR, ER stress and BiP chaperone systems, we discover that the interaction of BiP with the luminal domains of UPR proteins IRE1 and PERK switch...

2010年7月6日 · Here we show that the UPR matches its output to the magnitude of the stress by regulating the duration of Ire1 signaling. BiP binding to Ire1 serves to desensitize Ire1 to low levels of stress and promotes its deactivation when favorable folding conditions are restored to the ER.

2010年7月6日 · BiP binding to Ire1 serves to desensitize Ire1 to low levels of stress and promotes its deactivation when favorable folding conditions are restored to the ER. We propose that, mechanistically, BiP achieves these functions by sequestering inactive Ire1 molecules, thereby providing a barrier to oligomerization and activation, and a stabilizing ...

2019年12月24日 · We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1 LD that mediated BiP …

2020年7月20日 · Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) is a promising strategy to correct defects in endoplasmic reticulum (ER) proteostasis implicated in diverse...

2024年4月18日 · Our results demonstrate that the ER stress sensor IRE1 helps to sustain PERK expression during chronic ER stress. This occurs through a mechanism facilitated by IRE1-XBP1s signaling, with...

2012年4月6日 · In this model, the ATP bound form of BiP is required to bind IRE1/PERK and the ADP bound form releases from the complex. The inherent ATPase activity of BiP may then result in BiP-IRE1 and BiP-PERK interactions that are dynamic, causing BiP to cycle off and back onto the ER stress transducers.

2022年8月1日 · Over the years, basic research has contributed to understanding stress sensing and activation of IRE1 through three models, competitive or allosteric dissociation of BiP, and direct substrate binding to IRE1 itself.

ERdj4 associates with IRE1 LD and recruits BiP through the stimulation of ATP hydrolysis, forcibly disrupting IRE1 dimers. Unfolded proteins compete for BiP and restore IRE1 LD to its default, dimeric, and active state. These observations establish BiP and its J domain co-chaperones as key regulators of the UPR.

In response to ER stress, BiP (Binding immunoglobulin protein) dissociates with IRE1a (Inositol-requiring kinase 1) and binds to unfolded proteins as a molecular chaperone in helping maintain their correct structure. Co-related to BiP’s dissociation, IRE1a oglimerizes and activated its endoribonuclease domain by transautophosphorylation.