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CLC number: Q257

On-line Access: 2017-01-03

Received: 2016-03-15

Revision Accepted: 2016-07-18

Crosschecked: 2016-12-12

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Han-dong Fan

http://orcid.org/0000-0001-7040-7744

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.1 P.1-14

10.1631/jzus.B1600043


Molecular signal networks and regulating mechanisms of the unfolded protein response


Author(s):  Jing Gong, Xing-zhi Wang, Tao Wang, Jiao-jiao Chen, Xiao-yuan Xie, Hui Hu, Fang Yu, Hui-lin Liu, Xing-yan Jiang, Han-dong Fan

Affiliation(s):  Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China; more

Corresponding email(s):   fanhandong@whu.edu.cn

Key Words:  Unfolded protein response, Endoplasmic reticulum (ER) stress, Mechanism, Signal networks, Homeostasis


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Jing Gong, Xing-zhi Wang, Tao Wang, Jiao-jiao Chen, Xiao-yuan Xie, Hui Hu, Fang Yu, Hui-lin Liu, Xing-yan Jiang, Han-dong Fan. Molecular signal networks and regulating mechanisms of the unfolded protein response[J]. Journal of Zhejiang University Science B, 2017, 18(1): 1-14.

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author="Jing Gong, Xing-zhi Wang, Tao Wang, Jiao-jiao Chen, Xiao-yuan Xie, Hui Hu, Fang Yu, Hui-lin Liu, Xing-yan Jiang, Han-dong Fan",
journal="Journal of Zhejiang University Science B",
volume="18",
number="1",
pages="1-14",
year="2017",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600043"
}

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%T Molecular signal networks and regulating mechanisms of the unfolded protein response
%A Jing Gong
%A Xing-zhi Wang
%A Tao Wang
%A Jiao-jiao Chen
%A Xiao-yuan Xie
%A Hui Hu
%A Fang Yu
%A Hui-lin Liu
%A Xing-yan Jiang
%A Han-dong Fan
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 1
%P 1-14
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer

TY - JOUR
T1 - Molecular signal networks and regulating mechanisms of the unfolded protein response
A1 - Jing Gong
A1 - Xing-zhi Wang
A1 - Tao Wang
A1 - Jiao-jiao Chen
A1 - Xiao-yuan Xie
A1 - Hui Hu
A1 - Fang Yu
A1 - Hui-lin Liu
A1 - Xing-yan Jiang
A1 - Han-dong Fan
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 1
SP - 1
EP - 14
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -


Abstract: 
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum (ER). One of the primary mechanisms is the unfolded protein response (UPR). In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein (BiP) interacts with the three sensors (protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1α (IRE1α)). Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR)-phospholipase C-γ (PLCγ)-mammalian target of rapamycin complex 1 (mTORC1) pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IRE1α also can be activated by activated RAC-alpha serine/threonine-protein kinase (AKT). A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species (ROS), Ca2+ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription 3 (STAT3), and P38, when cellular damage exceeds the capacity of this adaptive response.

内质网应激的信号通路以及调控机制

概要:文章阐述了内质网应激信号通路及其调控机制;补充了最新的调控通路;探讨了内质网应激与肿瘤发生和细胞凋亡的关系。同时将内质网信号通路全面概括到一张图中,综合阐述了未折叠蛋白反应(UPR)的调控机制,并把内质网应激与细胞凋亡、肿瘤发生关联到一起,方便读者更好地了解与学习内质网应激。
关键词:未折叠蛋白;内质网应激;调控机制;信号通路;稳态

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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