scholarly journals Critical Role of Activating Transcription Factor 4 in the Anabolic Actions of Parathyroid Hormone in Bone

PLoS ONE ◽  
2009 ◽  
Vol 4 (10) ◽  
pp. e7583 ◽  
Author(s):  
Shibing Yu ◽  
Renny T. Franceschi ◽  
Min Luo ◽  
Jie Fan ◽  
Di Jiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Parathyroid Hormone ◽  
Critical Role ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4

2011 ◽  
Vol 435 (2) ◽  
pp. 431-439 ◽  
Author(s):  
Hyun Kook Cho ◽  
Kyu Jin Cheong ◽  
Hye Young Kim ◽  
JaeHun Cheong
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Critical Role ◽  
Activating Transcription Factor 4 ◽  
B Virus ◽  
Activating Transcription Factor ◽  
Transcription Factor 4 ◽  
Cox2 Expression

Chronic hepatitis B is a disease of the liver that can progress to cirrhosis and liver cancer. The HBx (hepatitis B virus X) protein of hepatitis B virus is a multifunctional regulator that induces ER (endoplasmic reticulum) stress by previously unknown mechanisms. ER stress plays a critical role in inflammatory induction and COX2 (cyclo-oxygenase 2) is an important mediator of this inflammation. In the present study, we demonstrate the molecular mechanisms of HBx on induction of ER stress and COX2 expression. In addition, HBx reduced expression of enzymes which are involved in mitochondrial β-oxidation of fatty acids and the mitochondrial inner membrane potential. The reduction in intracellular ATP levels by HBx induced the unfolded protein response and COX2 expression through the eIF2α (eukaryotic initiation factor 2α)/ATF4 (activating transcription factor 4) pathway. We confirmed that ATF4 binding to the COX2 promoter plays a critical role in HBx-mediated COX2 induction. The results of the present study suggest that HBV infection contributes to induction of hepatic inflammation through dysfunction of cellular organelles including the ER and mitochondria.

scholarly journals Induction of autophagy through the activating transcription factor 4 (ATF4)-dependent amino acid response pathway in maternal skeletal muscle may function as the molecular memory in response to gestational protein restriction to alert offspring to maternal nutrition

2015 ◽  
Vol 114 (4) ◽  
pp. 519-532 ◽  
Author(s):  
Huan Wang ◽  
Gabriel J. Wilson ◽  
Dan Zhou ◽  
Stéphane Lezmi ◽  
Xiuwen Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Amino Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Protein Restriction ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

The aim of the present study was to investigate the mechanistic basis of protein deficiency during pregnancy in mother that is transduced to offspring. To this end, timed-pregnant Sprague–Dawley rats were fed either a control (20 % of energy from protein) or low-protein (LP, 8 % of energy from protein) diet during gestation. Tissues were collected after delivery from rat dams, and skeletal muscle was collected at postnatal day 38 from the offspring. Quantitative RT-PCR and Western blot analyses were performed to determine mRNA and protein levels. Histological analysis was performed to evaluate myofibre size. LP dams gained significantly less weight during pregnancy, developed muscle atrophy, and had significantly lower circulating threonine and histidine levels than control dams. The mRNA expression of the well-known amino acid response (AAR) pathway-related target genes was increased only in the skeletal muscle of LP dams, as well as the protein expression levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α). The mRNA expression of autophagy-related genes was significantly increased in the skeletal muscle of LP dams. Moreover, the mRNA expression of genes involved in both AAR and autophagy pathways remained elevated and was memorised in the muscle of LP offspring that consumed a post-weaning control diet. Additionally, the LP diet increased an autophagy marker, microtubule-associated proteins 1A/1B light chain 3B (LC3B) protein expression in the skeletal muscle of rat dams, consistent with the initiation of autophagy. The LP diet further increased ATF4 binding at the predicted regions of AAR and autophagy pathway-related genes. Increased binding of ATF4 unveils the crucial role of ATF4 in the activation of autophagy in response to protein restriction. Our data suggest that molecular changes in maternal muscle are memorised in the offspring long after gestational protein restriction, reinforcing the role of maternal signalling in programming offspring health.

scholarly journals Role of activating transcription factor 4 in the hepatic response to amino acid depletion by asparaginase

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Rana J. T. Al-Baghdadi ◽  
Inna A. Nikonorova ◽  
Emily T. Mirek ◽  
Yongping Wang ◽  
Jinhee Park ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Activating Transcription Factor 4 ◽  
Amino Acid Depletion ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

Role of Activating Transcription Factor-4 in 24-Hour Rhythm of Serotonin Transporter Expression in the Mouse Midbrain

2012 ◽  
Vol 82 (2) ◽  
pp. 264-270 ◽  
Author(s):  
Kentarou Ushijima ◽  
Satoru Koyanagi ◽  
Yuuki Sato ◽  
Takamitsu Ogata ◽  
Naoya Matsunaga ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Serotonin Transporter ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Transcription Factor 4 ◽  
Transporter Expression

scholarly journals Activating Transcription Factor 4 Is Translationally Regulated by Hypoxic Stress

2004 ◽  
Vol 24 (17) ◽  
pp. 7469-7482 ◽  
Author(s):  
Jaime D. Blais ◽  
Vasilisa Filipenko ◽  
Meixia Bi ◽  
Heather P. Harding ◽  
David Ron ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Microarray Analysis ◽  
Initiation Factor ◽  
Hypoxic Stress ◽  
Unfolded Protein ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Transcription Factor 4

ABSTRACT Hypoxic stress results in a rapid and sustained inhibition of protein synthesis that is at least partially mediated by eukaryotic initiation factor 2α (eIF2α) phosphorylation by the endoplasmic reticulum (ER) kinase PERK. Here we show through microarray analysis of polysome-bound RNA in aerobic and hypoxic HeLa cells that a subset of transcripts are preferentially translated during hypoxia, including activating transcription factor 4 (ATF4), an important mediator of the unfolded protein response. Changes in mRNA translation during the unfolded protein response are mediated by PERK phosphorylation of the translation initiation factor eIF2α at Ser-51. Similarly, PERK is activated and is responsible for translational regulation under hypoxic conditions, while inducing the translation of ATF4. The overexpression of a C-terminal fragment of GADD34 that constitutively dephosphorylates eIF2α was able to attenuate the phosphorylation of eIF2α and severely inhibit the induction of ATF4 in response to hypoxic stress. These studies demonstrate the essential role of ATF4 in the response to hypoxic stress, define the pathway for its induction, and reveal that GADD34, a target of ATF4 activation, negatively regulates the eIF2α-mediated inhibition of translation. Taken with the concomitant induction of additional ER-resident proteins identified by our microarray analysis, this study suggests an important integrated response between ER signaling and the cellular adaptation to hypoxic stress.

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