Results 51 to 60 of about 15,652 (205)

Sensor dimer disruption as a new mode of action to block the IRE1-mediated unfolded protein response

Computational and Structural Biotechnology Journal, 2022
The unfolded protein response (UPR) is activated to cope with an accumulation of improperly folded proteins in the Endoplasmic reticulum (ER). The Inositol requiring enzyme 1α (IRE1α) is the most evolutionary conserved transducer of the UPR.
Kosala N. Amarasinghe, Diana Pelizzari-Raymundo, Antonio Carlesso, Eric Chevet, Leif A. Eriksson, Sayyed Jalil Mahdizadeh   +5 more
doaj   +1 more source

The IRE1‐XBP1s Axis Drives Inflammatory Osteolysis by Regulating a 5‐HT Dependent Endogenous Anti‐Autophagy Mechanism

Advanced Science, EarlyView.
A previously unrecognized IRE1‐XBP1s‐Slc6a4 signaling axis links endoplasmic reticulum stress to serotonin metabolism, autophagy, and inflammatory osteoclastogenesis. By promoting intracellular serotonin uptake and reducing endogenous 3‐methyladenine accumulation, this pathway accelerates inflammatory bone destruction and provides a promising ...
Pengchao Yang, Binxiang Zhu, Yuzhi He, Yang Tian, Honglei Kang, Shian Hu, Pengju Wang, Yong Xu, Zhuowei Lei, Peijun Qi, Hao Yang, Yang Lin, Yimin Dong, Feng Li, Hanfeng Guan   +14 more
wiley   +1 more source

Aberrant GRP78 Phase Transition Sustains Endothelial IRE1α Signaling and Drives Blood–Brain Barrier Failure in Cerebral Amyloid Angiopathy

Advanced Science, EarlyView.
Vascular Aβ40 corrupts GRP78 phase behavior in brain endothelial cells, sustaining IRE1α–TRAF2–JNK signaling and driving apoptosis, tight junction loss, and blood–brain barrier failure in cerebral amyloid angiopathy. Pharmacological IRE1α inhibition restores vascular integrity, reduces leakage, and improves functional outcomes, revealing a targetable ...
Honglin Zheng, Qiang Li, Haiyang Luo, Yapei Yuan, Na Zhang, Yongting Lu, Suying Duan, Jieshi Zhong, Hang Zhang, Chenyang Liu, Yaochong Zhang, Wenzhuo Zhao, Yaxuan Song, Tuo Wang, Si Yan, Yapeng Li, Han Liu, Yuan Gao, Zongping Xia, Yuming Xu   +19 more
wiley   +1 more source

Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. [PDF]

PLoS Pathogens, 2011
In eukaryotic cells, the unfolded protein response (UPR) pathway plays a crucial role in cellular homeostasis of the endoplasmic reticulum (ER) during exposure to diverse environmental conditions that cause ER stress. Here we report that the human fungal
Seon Ah Cheon, Kwang-Woo Jung, Ying-Lien Chen, Joseph Heitman, Yong-Sun Bahn, Hyun Ah Kang   +5 more
doaj   +1 more source

The IRE1 Inhibitor Kira6 Curtails The Inflammatory Trait Of Immunogenic Anticancer Treatments By Targeting Hsp60 Independent Of IRE1 [PDF]

, 2020
ABSTRACT Cellular stress evoked by immunogenic anticancer treatments engaging the unfolded protein response (UPR) can elicit inflammation with conflicting therapeutic outcomes. To define cell-autonomous mechanisms coupling the UPR to molecular mediators of inflammation, we profiled the transcriptome of cancer cells responding to ...
Rufo Nicole, Korovesis Dimitris, Van Eygen Sofie, Rita Derua, Abhishek D Garg, Finotello Francesca, Vara-Perez Monica, Rožanc Jan, Dewaele Michael, Peter A de Witte, Leonidas G Alexopoulos, Sophie Janssens, Sinkkonen Lasse, Sauter Thomas, Steven HL Verhelst, Agostinis Patrizia   +15 more
openaire   +1 more source

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

Advanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu, Hongyuan Zhang, Tayyiba Azam, Susanne S. Hille, Yingjuan Liu, Min Zi, Jiaqing Lang, He Yu, Yujia Cao, Bernard D. Keavney, Tamer M. A. Mohamed, Jessica M. Miller, Riham R. E. Abouleisa, Ming Xu, Elizabeth J. Cartwright, Oliver J. Müller, Ming Lei, Xin Wang   +17 more
wiley   +1 more source

A nonenzymatic dependency on inositol-requiring enzyme 1 controls cancer cell cycle progression and tumor growth.

PLoS Biology
Endoplasmic-reticulum resident inositol-requiring enzyme 1α (IRE1) supports protein homeostasis via its cytoplasmic kinase-RNase module. Known cancer dependency on IRE1 entails its enzymatic activation of the transcription factor XBP1s and of regulated ...
Iratxe Zuazo-Gaztelu, David Lawrence, Ioanna Oikonomidi, Scot Marsters, Ximo Pechuan-Jorge, Catarina J Gaspar, David Kan, Ehud Segal, Kevin Clark, Maureen Beresini, Marie-Gabrielle Braun, Joachim Rudolph, Zora Modrusan, Meena Choi, Wendy Sandoval, Mike Reichelt, David C DeWitt, Pekka Kujala, Suzanne van Dijk, Judith Klumperman, Avi Ashkenazi   +20 more
doaj   +1 more source

Xbp1-Independent Ire1 Signaling Is Required for Photoreceptor Differentiation and Rhabdomere Morphogenesis in Drosophila

Cell Reports, 2013
The unfolded protein response (UPR) is composed by homeostatic signaling pathways that are activated by excessive protein misfolding in the endoplasmic reticulum.
Dina S. Coelho, Fatima Cairrão, Xiaomei Zeng, Elisabete Pires, Ana V. Coelho, David Ron, Hyung Don Ryoo, Pedro M. Domingos   +7 more
doaj   +1 more source

Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands

Nature Communications, 2020
The RNase activity of Inositol-Requiring Enzyme 1 (IRE1) can be allosterically regulated by ATP-competitive inhibitors of the IRE1 kinase domain. Here, the authors identify ATP-competitive IRE1 RNase activators with improved selectivity and cellular ...
Elena Ferri, Adrien Le Thomas, Heidi Ackerly Wallweber, Eric S. Day, Benjamin T. Walters, Susan E. Kaufman, Marie-Gabrielle Braun, Kevin R. Clark, Maureen H. Beresini, Kyle Mortara, Yung-Chia A. Chen, Breanna Canter, Wilson Phung, Peter S. Liu, Alfred Lammens, Avi Ashkenazi, Joachim Rudolph, Weiru Wang   +17 more
doaj   +1 more source

Modulation of Animal Gut Health by Milk Oligosaccharide

Animal Research and One Health, EarlyView.
This review summarizes the composition and structural characteristics of MOs across different mammalian species, and elucidates their roles and mechanisms in maintaining intestinal homeostasis by regulating gut microbiome and enhancing intestinal chemical, physical and immune barriers.
Ningtao Chen, Nana Jing, Shiyu Tao, Mingyue Fei, Wentao Lv, Hua Yang, Yingping Xiao, Haiqin Wu   +7 more
wiley   +1 more source