未折叠蛋白反应
内质网
细胞生物学
信号转导
生物
神经退行性变
激酶
细胞应激反应
生物化学
战斗或逃跑反应
医学
基因
病理
疾病
作者
Natalia Siwecka,Wioletta Rozpędek‐Kamińska,Adam Wawrzynkiewicz,Dariusz Pytel,J. Alan Diehl,Ireneusz Majsterek
出处
期刊:Biomedicines
[MDPI AG]
日期:2021-02-05
卷期号:9 (2): 156-156
被引量:62
标识
DOI:10.3390/biomedicines9020156
摘要
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-apoptotic cellular responses, which are strictly related to numerous human pathologies. Among others, IRE1 activity has been confirmed to be increased in cancer, neurodegeneration, inflammatory and metabolic disorders, which are associated with an accumulation of misfolded proteins within ER lumen and the resulting ER stress conditions. Emerging evidence suggests that genetic or pharmacological modulation of IRE1 may have a significant impact on cell viability, and thus may be a promising step forward towards development of novel therapeutic strategies. In this review, we extensively describe the structural analysis of IRE1 molecule, the molecular dynamics associated with IRE1 activation, and interconnection between it and the other branches of the UPR with regard to its potential use as a therapeutic target. Detailed knowledge of the molecular characteristics of the IRE1 protein and its activation may allow the design of specific kinase or RNase modulators that may act as drug candidates.
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