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The ATF4 gene is located in the 22q13.1 region of human chromosome 22 and encodes activating transcription factor 4 (ATF4), which belongs to the basic leucine zipper (bZIP) family of transcription factors. ATF4 is a stress-responsive transcription factor, with its bZIP domain containing a basic DNA-binding region and a leucine zipper dimerization interface, and a nuclear localization signal mediating its translocation into the nucleus. Its molecular weight is approximately 38 kDa and it is ubiquitously expressed across human tissues, with relatively high expression in metabolically active tissues such as liver, kidney, and brain. As a master regulator of the integrated stress response, ATF4 is translationally induced under diverse stress conditions, including amino acid deprivation, endoplasmic reticulum stress, hypoxia, and oxidative stress, through phosphorylation of eIF2α and re-initiation at upstream open reading frames. Activated ATF4 binds cAMP response elements and related recognition sites to regulate genes involved in amino acid metabolism, antioxidant defense, and the balance between cell survival and apoptosis. This gene is subject to intricate translational control mediated by upstream open reading frames in its 5' untranslated region, which restrict basal ATF4 synthesis while permitting rapid induction under stress. ATF4 heterodimerizes with other bZIP partners, including C/EBP family members, and its interaction with the scaffold protein DISC1 modulates its transcriptional activity in neurons. Germline inactivation of ATF4 in mice causes embryonic lethality associated with severe anemia and defective lens development, underscoring its essential roles in hematopoiesis and organogenesis. Therefore, ATF4 is regarded as an important molecular target for studying stress signaling, translational regulation, and the transcriptional control of cellular adaptation. Its functional analysis provides valuable tools for understanding the molecular mechanisms of the integrated stress response and cell fate determination.
Fig. 1 Structure of ATF4 and its dimerization with CREB/β.1
The functional spectrum of ATF4 is extensive and is continuously expanding:
Creative Biolabs offers a series of high-quality ATF4 recombinant protein products, suitable for structural and functional research. Relying on the independently developed MemDX™ recombinant protein technology platform, ATF4 proteins can be prepared through various expression systems, including in vitro prokaryotic and eukaryotic expression systems. These rigorously validated protein products, such as recombinant human ATF4 protein from various expression systems, can be used in ELISA, antibody screening and identification, DNA-binding experiments, and functional research, providing reliable tools for researchers to analyze the transcriptional regulatory mechanisms of ATF4.
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Constructing a robust cell model is crucial for the study of ATF4-mediated stress-responsive transcription. As a bZIP transcription factor that governs the integrated stress response, the expression level and activity of ATF4 directly influence the cellular response to diverse stress stimuli and the balance between adaptation and apoptosis. Different genetic backgrounds, translational regulation, or post-translational modifications may lead to significant differences in ATF4 transcriptional output and downstream target gene expression. Creative Biolabs offers customized ATF4 stable transfection cell models, covering wild-type and various functionally characterized forms. These models stably express the target protein in the nucleus, and are suitable for studies on transcriptional activity, stress-response signaling, target gene expression analysis, and assessment of cell survival under stress conditions, providing a reliable and reproducible platform for exploring the transcriptional mechanism, structure-function relationship, and stress regulatory network of ATF4. Our technology ensures correct protein localization in the nucleus, facilitating your research.
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Creative Biolabs offers highly specific recombinant antibodies targeting ATF4, produced using advanced recombinant antibody technology. Compared to traditional antibodies, these recombinant antibodies demonstrate superior performance in terms of specificity, sensitivity, and batch-to-batch consistency. They can also be modified and labeled in various ways. Our ATF4 recombinant antibodies support a wide range of applications, including Western Blot, ELISA, flow cytometry, immunofluorescence, immunocytochemistry, immunohistochemistry, and immunoprecipitation, and can be used to detect differences in ATF4 expression levels in various tissues or cell sources, analyze its nuclear localization, and conduct related research such as protein-protein interaction and transcriptional pathway analysis. These antibodies provide reliable detection tools for the structural analysis, functional study of ATF4, and the analysis of its regulation in the integrated stress response network.
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In addition to the standard products, Creative Biolabs also offers professional customized services for ATF4. ATF4 is subject to complex translational and post-translational regulation that influences its stability and transcriptional activity. These regulatory features present specific requirements in areas such as recombinant protein production, antigen design, and functional characterization. Leveraging our technology platform, we can assist you in completing the following customized projects:
ATF4 functions as a master transcription factor of the integrated stress response, where it is translationally induced upon eIF2α phosphorylation and binds cAMP response elements to regulate genes involved in amino acid metabolism, antioxidant defense, and the balance between cell survival and apoptosis. Its expression is tightly controlled by upstream open reading frames that maintain low basal levels while enabling rapid induction under stress. It serves as an important model for investigating stress signaling and the molecular mechanisms of transcriptional control.
ATF4 lies at the convergence point of multiple stress-sensing pathways, including amino acid deprivation, endoplasmic reticulum stress, hypoxia, and oxidative stress, and its activity determines whether cells adapt and survive or undergo apoptosis. It is implicated in diverse pathological contexts, including cancer, metabolic disorders, and neurodegenerative diseases. Its intricate regulation by upstream open reading frames and heterodimerization with other bZIP proteins makes ATF4 a valuable system for studying translational control and transcription factor biology.
They are not. All ATF4 products and services provided by Creative Biolabs are exclusively for research applications and may not be employed for any diagnostic, prophylactic, or therapeutic purpose in humans.
Multiple product formats are available, encompassing recombinant ATF4 proteins, stable cell models expressing ATF4, high-quality recombinant anti-ATF4 antibodies, as well as comprehensive customized research services.