Both transcriptional regulation and translational control of ATF4 are central to the integrated stress response.
TLDR
This study addressed the underlying mechanism for variable expression of ATF4 in response to eIF2∼P during different stress conditions and the biological significance of omission of enhanced ATF4 function, and showed that in addition to translational control, ATF4 expression is subject to transcriptional regulation.About:
This article is published in Journal of Biological Chemistry.The article was published on 2010-10-22 and is currently open access. It has received 202 citations till now. The article focuses on the topics: Integrated stress response & Unfolded protein response.read more
Citations
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Journal ArticleDOI
The integrated stress response.
Karolina Pakos-Zebrucka,Izabela Koryga,Katarzyna Mnich,Mila Ljujic,Afshin Samali,Adrienne M. Gorman +5 more
TL;DR: Current understanding of the ISR signaling is reviewed and how it regulates cell fate under diverse types of stress is reviewed.
Journal ArticleDOI
Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine
Kook Hwan Kim,Yeon Taek Jeong,Hyunhee Oh,Seonghun Kim,Jae Min Cho,Yo-Na Kim,Su Sung Kim,Dohoon Kim,Kyu Yeon Hur,Hyoung Kyu Kim,Tae-Hee Ko,Jin Han,Hong Lim Kim,Jin Kim,Sung Hoon Back,Masaaki Komatsu,Hsiuchen Chen,David C. Chan,Morichika Konishi,Nobuyuki Itoh,Cheol Soo Choi,Myung-Shik Lee,Myung-Shik Lee +22 more
TL;DR: It is suggested that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone the authors consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance.
Journal ArticleDOI
The eIF2α kinases: their structures and functions
TL;DR: While significant sequence similarity exists between the eIF2α kinases in their kinase domains, underlying their common role in phosphorylating eif2α, additional unique features determine the regulation of these four proteins, that is, what signals activate them.
Journal ArticleDOI
The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress.
TL;DR: Advancing molecular insight into the transition of tumor cells from adaptation to apoptosis under hypoxia-induced ER stress may provide answers on how to overcome the limitations of current anti-tumor therapies.
Journal ArticleDOI
miR-214 targets ATF4 to inhibit bone formation
Xiaogang Wang,Baosheng Guo,Baosheng Guo,Qi Li,Jiang Peng,Zhijun Yang,Aiyuan Wang,Dong Li,Zhibo Hou,Ke Lv,Guanghan Kan,Hongqing Cao,Heng Wu,Heng Wu,Jinping Song,Xiaohua Pan,Qiao Sun,Shukuan Ling,Yuheng Li,Mu Zhu,Pengfei Zhang,Songlin Peng,Xiaoqing Xie,Tao Tang,An Hong,Zhaoxiang Bian,Yanqiang Bai,Aiping Lu,Yinghui Li,Fuchu He,Ge Zhang,Ge Zhang,Yingxian Li +32 more
TL;DR: Elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures, and in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomIR-214, and mi R-214 directly targeted ATF4 to inhibit osteoblasts activity.
References
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Journal ArticleDOI
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more
TL;DR: Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids.
Journal ArticleDOI
Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells
Heather P. Harding,Isabel Novoa,Yuhong Zhang,Huiqing Zeng,Ronald C. Wek,Matthieu Schapira,David Ron +6 more
TL;DR: Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) are activated in stressed cells and negatively regulate protein synthesis, resulting in the induction of the downstream gene CHOP (GADD153).
Journal ArticleDOI
An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress
Heather P. Harding,Yuhong Zhang,Huiquing Zeng,Isabel Novoa,Phoebe D. Lu,Marcella Calfon,Navid Sadri,Chi Yun,Brian Popko,Richard S. Paules,David F. Stojdl,John C. Bell,Thore Hettmann,Jeffrey M. Leiden,David Ron +14 more
TL;DR: A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress.
Journal ArticleDOI
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
TL;DR: Recent advances in understanding of the molecular structures and biochemical functions of the translation initiation machinery are described and key strategies that mediate general or gene-specific translational control are summarized, particularly in mammalian systems.
Journal ArticleDOI
The mammalian unfolded protein response
TL;DR: In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure as mentioned in this paper.
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