The highly dynamic changes in microglia necessary to achieve a rapid neuroinflammatory response require a supply of energy from mitochondrial respiration, which leads to the accumulation of unfolded mitochondrial proteins. We previously reported that...
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we recount the evidence identifying the basic leucine z...
Cancer cell survival, function and fate strongly depend on endoplasmic reticulum (ER) proteostasis. Although previous studies have implicated the ER stress signaling network in all stages of cancer development, its role in cancer metastasis remains t...
Natural killer (NK) cells are an important innate defense against malignancies, and exogenous sources of NK cells have been developed as anti-cancer agents. Nevertheless, the apparent limitations of NK cells in clearing cancers have suggested that th...
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults and is characterized by aggressive progression and substantial molecular and clinical heterogeneity. Despite advances in immunochemotherapy...
Steroidogenic Factor 1 (SF-1/NR5A1), an orphan nuclear receptor, is important for sexual differentiation and the development of multiple endocrine organs, as well as cell proliferation in cancer cells. Activating transcription factor 3 (ATF3) is a tr...
Spermatogenesis is a metabolically intensive process that is highly sensitive to perturbations in proteostasis. The integrated stress response (ISR) and its central effector, ATF4, orchestrate adaptive responses to maintain cellular homeostasis under...
Activating transcription factor 3 (ATF3), a transcription factor and acute stress sensor, is rapidly induced by a variety of pathophysiological signals and is essential in the complex processes in cellular stress response. FOXP3, a well-known breast...
STK26 is highly expressed in colorectal cancer (CRC) and linked to tumorigenesis. Although implicated in unfolded protein response (UPR)-related oxidative stress, whether STK26 regulates CRC occurrence via the ATF6 pathway—a classic UPR branch...
Activating transcription factor 6α (ATF6α) is an endoplasmic reticulum protein known to participate in unfolded protein response (UPR) during ER stress in mammals. Herein, we show that in mouse C2C12 myoblasts induced to differentiate, AT...
Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. T...
Impaired clearance of all-trans-retinal (atRAL) during the visual cycle leads to retinal degeneration, which is closely associated with autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (dry AMD). Transient activa...
SUMOylation plays an important role in regulating a wide range of cellular processes. Previously, we showed that ATF3, a stress response mediator, can be SUMOylated and lysine 42 is the major SUMO site. However, the significance of ATF3 SUMOylation i...
Activating transcription factor 4 (ATF4) is a master transcription factor of integrated stress response (ISR), an evolutionarily conserved intracellular signaling network that helps the cell, tissue, and organism to adapt to various unpredictable env...
Epigenetic modifications are critical for cell differentiation and growth. As a regulator of H3K9 methylation, Setdb1 is implicated in osteoblast proliferation and differentiation. The activity and nucleus localization of Setdb1 are regulated by its...
The late embryonic mouse lens requires the transcription factor ATF4 for its survival although the underlying mechanisms were unknown. Here, RNAseq analysis revealed that E16.5 Atf4 null mouse lenses downregulate the mRNA levels of lens epithelial ma...
Activating transcription factor 4 (ATF4) is a DNA-binding protein widely generated in mammals, which has two biological characteristics that bind the cAMP response element (CRE). The mechanism of ATF4 as a transcription factor in gastric cancer affec...
There are more than 2000 transcription factors in eukaryotes, many of which are subject to complex mechanisms fine-tuning their activity and their transcriptional programs to meet the vast array of conditions under which cells must adapt to thrive an...
The heart exhibits incredible plasticity in response to both environmental and genetic alterations that affect workload. Over the course of development, or in response to physiological or pathological stimuli, the heart responds to fluctuations in wo...
HER2 (human epidermal growth factor receptor 2) activation is critical in breast cancer development. HER2 promotes cell proliferation, angiogenesis, survival, and metastasis by activation of PI3K/Akt, Ras/MEK/ERK, and JAK/STAT pathways. However, beyo...
Activating transcription factor 3 (ATF3) has been identified as a negative regulator of osteoblast differentiation in in vitro study. However, it was not associated with osteoblast differentiation in in vivo study. To provide an understanding of the...
In response to cellular stresses, activating transcriptional factor 4 (ATF4) regulates the expression of both stress-relieving genes and apoptosis-inducing genes, eliciting cell fate determination. Since pharmacological activation of ATF4 exerts pote...
Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Human ccRCCs have increased glycolytic metabolism and decreased mitochondrial oxidative metabolism relative to normal kidneys. Our research using...
Transcription factors are pivotal regulators in the cellular life process. Activating transcription factor 3 (ATF3), a member of the ATF/CREB (cAMP response element-binding protein) family, plays a crucial role as cells respond to various stresses an...
Osthole is a natural coumarin derivative found in several medicinal plants, including Cnidium monnieri and Angelica pubescens. It has been studied for its various biological properties, such as anti-inflammatory, neuroprotective, osteogenic, cardiopr...
Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor...
Activating transcription factor-6 α (ATF6) is one of the three main sensors and effectors of the endoplasmic reticulum (ER) stress response and, as such, it is critical for protecting the heart and other tissues from a variety of environmental...
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by fibroblast activation, excessive deposition of extracellular matrix, and progressive scarring; the pathogenesis remains elusive. The present study explored the...
Fungal basic leucine zipper (bZIP) transcription factors mediate responses to oxidative stress. The ability to regulate stress response pathways in Aspergillus spp. was postulated to be an important virulence-associated cellular process, because it h...
Cadmium is an exceptionally toxic industrial and environmental pollutant classified as a human carcinogen. In order to provide insight into how we can keep our environment safe from cadmium contamination and prevent the accumulation of it in the food...
The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a pote...
This study aims to enhance membrane protein production in HEK293T cells through genetic modification. HEK293T cells are used for recombinant protein and viral vector production due to their human origin and post-translational modification capabilitie...
Childhood obesity is a complex pathology that triggers early vascular damage through endoplasmic reticulum (ER) stress and fibrinolytic imbalance; however, the role of the ATF6/PLAT regulatory axis in this process has not yet been fully elucidated. T...
Carnosic acid (CA) is a phytochemical found in some dietary herbs, such as Rosmarinus officinalis L., and possesses antioxidative and anti-microbial properties. We previously demonstrated that CA functions as an activator of nuclear factor, erythroid...
Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree...
Cells are continuously exposed to physiological and environmental stressors that disrupt homeostasis, triggering adaptive mechanisms such as the integrated stress response (ISR). A central feature of ISR is the selective translation of activating tra...
Basal-like breast cancer (BLBC) is an aggressive and deadly subtype of human breast cancer that is highly metastatic, displays stem-cell like features, and has limited treatment options. Therefore, developing and characterizing preclinical mouse mode...
Background: Nod-like receptor protein 3 (NLRP3) inflammasome is a crucial contributor in the inflammatory process during cerebral ischemia/reperfusion (I/R) injury. ATF4 plays a pivotal role in the pathogenesis of cerebral I/R injury, however, its fu...
Rpb11 subunit of RNA polymerase II of Eukaryotes is related to N-terminal domain of eubacterial α subunit and forms a complex with Rpb3 subunit analogous to prokaryotic α2 homodimer, which is involved in RNA polymerase assembly and promot...
Chronic treatment with acetaminophen (APAP) induces cysteine (Cys) and glutathione (GSH) deficiency which leads to adverse metabolic effects including muscle atrophy. Mammalian cells respond to essential amino acid deprivation through the phosphoryla...
Prostaglandin (PG) A2, a cyclopentenone PG, induced apoptosis in both HCT116 and HCT116 p53 −/− cells. Although PGA2-induced apoptosis in HCT116 cells was dependent on the p53-DR5 pathway, the mechanism underlying PGA2-induced apoptosis i...
The extracellular aggregation of destabilized transthyretin (TTR) variants is implicated in the onset and pathogenesis of familial TTR-related amyloid diseases. One strategy to reduce the toxic, extracellular aggregation of TTR is to decrease the pop...
Acetate esters, synthesized by alcohol acyltransferase (AATases) encoded primarily by the ATF1 gene, are pivotal for the desirable fruity aroma in fermented foods. However, the role and regulatory impact of ATF1 in solid-state fermented meat remain l...
It is necessary to find novel therapeutic strategies for obesity-related diabetic nephropathy (DN) that target both metabolic dysfunction and renal inflammation. ST32da derived from Salvia miltiorrhiza (a well-recognized Traditional Chinese Medicine)...
Liver fibrosis is a progressive and debilitating condition characterized by the excessive deposition of extracellular matrix proteins. Stellate cell activation, a major contributor to fibrogenesis, is influenced by Transforming growth factor (TGF-&be...
Arsenic is one of the most common environmental pollutants eliciting serious public health issues; however, it is also a well-recognized chemotherapeutic agent for acute promyelocytic leukemia. The association between arsenic exposure and lung diseas...
The risk of Aspergillus flavus contamination is expanding with global warming. Targeting the pathogenicity of A. flavus at its source and diminishing its colonization within the host may be a potential control strategy. Oxidative stress transcription...
A variety of cellular stresses lead to global translation attenuation due to phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2), which decreases the availability of the eIF2-GTP-Met-tRNAi ternary complex. However, a subset...
Activating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4...
Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is es...
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