Here we discover that IRE1α, the sensor of the unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex. ERAD-mediated IRE1α degradation occurs under basal conditions in a BiP-dependent manner, requires both the intramembrane hydrophilic residues of IRE1α and the lectin protein OS9, and is attenuated by ER stress.

ERAD的核心过程由Cdc48/p97/VCP提供能源，Cdc48是一个保守的六聚体II类AAA+ATP酶。除Hrd1外，有许多E3连接酶都显示可以参与介导错误/未折叠蛋白的泛素化，包括AMFR/gp78、TRC8/Rnf139、TEB4/MARCH-VI/Doa10/Rnf176、Rnf5/Rma1、Rnf170、Rnf185、TMEM129等，它们均为RING型E3酶。参与ERAD的E2 ...

2015年11月9日 · Here we discover that IRE1α, the sensor of the unfolded protein response (UPR), is a bona fide substrate of the Sel1L–Hrd1 ERAD complex. ERAD-mediated IRE1α degradation occurs under basal...

2020年8月8日 · Xbp1s进入细胞核后会启动一系列基因转录(如脂质合成、ERAD等)，从多个层次缓解内质网应激。 除此之外p-IRE1α可以通过RIDD过程促进mRNA的降解，减缓新生多肽链合成，降低内质网压力。

Endoplasmic reticulum (ER)-associated degradation (ERAD) represents a principle quality control mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unexplored.

Inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) is the most prominent and evolutionarily conserved unfolded protein response (UPR) signal transducer during endoplasmic reticulum functional upset (ER stress). A IRE1α signal pathway arbitrates yin and yang of cellular fate in objectionable conditions.

Inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) is the most prominent and evolutionarily conserved endoplasmic reticulum (ER) membrane protein. This transduces the signal of misfolded protein accumulation in the ER, named as ER stress, to the nucleus as “unfolded protein response (UPR).”

2019年12月6日 · Inositol-requiring enzyme 1 (IRE1) is an endoplasmic reticulum (ER)-resident transmembrane protein that senses ER stress and is evolutionarily conserved from yeast to humans. IRE1 possesses both Ser/Thr protein kinase and endoribonuclease (RNase) activities within its cytoplasmic domain and is activated through autophosphorylation and ...

2021年12月15日 · Inositol requiring enzyme 1 (IRE1) mitigates endoplasmic-reticulum (ER) stress by orchestrating the unfolded-protein response (UPR). IRE1 spans the ER membrane, and signals through a cytosolic...

2003年2月1日 · Using the secreted, normal α1-antitrypsin (A1AT) or a misfolded variant termed null Hong Kong (NHK), they demonstrate that expression of NHK protein stimulates both ERSE and UPRE reporters, and that the UPRE response is IRE dependent. Next, they employ NHK in its capacity as an ERAD substrate to examine the roles of IRE1 and EDEM in this process.