Atf4 Antibodies

Background

ATF4 belongs to the family of basic leucine zipper transcription factors and is mainly present in various cell types of eukaryotes. This protein plays a core role in integrating intracellular and extracellular signals such as endoplasmic reticulum stress, amino acid deficiency and oxidative stress, and coordinates cellular adaptability and survival mechanisms by regulating the expression of target genes. Especially in metabolic regulation, neuronal function and bone development, ATF4 plays a crucial role in maintaining cellular homeostasis. Its functional mechanism was initially gradually revealed in the study of stress response pathways and has now been confirmed to be the core medium for integrating stress responses. The multifunctional regulatory network of ATF4 has continuously become an important model for the study of cell stress biology and disease mechanisms, promoting the understanding of the role of transcriptional regulation in physiological balance.

Structure Function Application Advantage Our Products

Structure of Atf4

ATF4 is a basic leucine zipper (bZIP) transcription factor with a molecular weight of approximately 49 kDa. This value shows slight differences among different mammals, mainly due to the adaptive changes in the amino acid sequence of the regulatory domain.

Species	Human	Mouse	Rat	Bovine
Molecular Weight (kDa)	49.0	48.8	48.9	49.1
Primary Structural Differences	Contains the conserved bZIP domain and transcription activation domain	Highly homologous DNA binding area	Stress response areas were similar	Species-specific variation was found in the regulatory sequence

ATF4 is composed of 351 amino acids. Its primary structure forms a typical bZIP fold and specifically binds to DNA through the basic amino acid region at the carboxyl terminus. The core function of the protein depends on the leucine zipper dimerization domain composed of an α -helix, which allows ATF4 to form heterodimers with other bZIP proteins (such as members of the C/EBP family), thereby expanding its target gene regulatory spectrum. The N-terminal of a protein contains multiple phosphorylation sites, which can be activated by kinases (such as PERK) under stress conditions, thereby regulating its nuclear translocation and transcriptional activity.

Fig. 1:Post-translational Modifications of Human ATF4. Fig. 1 Post-translational Modifications of Human ATF4.¹

Key structural properties of ATF4:

Typical basic leucine zipper (bZIP) dimerization domain
Conserved DNA binding regions are rich in basic amino acids
Variable n-terminal transcription activation domain contains multiple phosphorylation site

Functions of Atf4

The main function of ATF4 is to serve as a core regulatory factor for integrating stress responses. However, it is also widely involved in a variety of physiological and pathological processes, including metabolic regulation, cell fate determination and bone development.

Function	Description
Integration of stress signals	ATF4 is activated by multiple signaling pathways such as endoplasmic reticulum stress, amino acid deficiency, and oxidative stress, coordinating the adaptive responses of cells.
Metabolic reprogramming	Regulate the expression of genes such as amino acid synthesis and transport, and antioxidant responses, and support survival and proliferation under stress in tumor cells.
Cell fate determination	Depending on the stress intensity and cell type, cell cycle arrest and autophagy can be induced to promote recovery, or apoptosis can be triggered to eliminate damaged cells.
Regulation of bone development	Plays a key role in osteoblast differentiation, and its dysfunction is closely related to many diseases in skeletal dysplasia.
Regulation of neuronal function	Involved in synaptic plasticity, learning and memory, and neurodegenerative processes.

Unlike "immediate response" transcription factors, the regulation of ATF4 typically manifests as continuous and comprehensive transcriptional reprogramming, which reflects its core role as a decision-maker of cell fate rather than a fast-response primary effector factor.

Applications of Atf4 and Atf4 Antibody in Literature

1. He, Feng, et al. "ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis." Journal of hepatology 79.2 (2023): 362-377. https://doi.org/10.1016/j.jhep.2023.03.016

The article indicates that in the MUP-uPA mouse model, hepatocellular specific deletion of ATF4 enhances ferroptosis sensitivity by reducing the expression of SLC7A11, exacerbating liver injury, inflammation and the development of hepatocellular carcinoma. Replenishing SLC7A11 can reverse this process. Studies have shown that ATF4 exerts a protective effect in normal liver cells by inhibiting ferroptosis, suggesting that its activation or inhibition of ferroptosis may prevent liver cancer.

2. Han, Shuting, et al. "Targeting ATF4-dependent pro-survival autophagy to synergize glutaminolysis inhibition." Theranostics 11.17 (2021): 8464. https://doi.org/10.7150/thno.60028

The article indicates that in colorectal cancer, inhibiting glutamine decomposition stabilizes and upregulates ATF4 by reducing the m6A modification of ATF4 mRNA. ATF4 inhibits mTOR by transcriptionally activating DDIT4, thereby inducing protective autophagy and weakening the anti-tumor effect of the therapy. Targeting ATF4-mediated autophagy can enhance the therapeutic effect of glutamine decomposition inhibition.

3. Gao, Ruize, et al. "YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis." EMBO molecular medicine 13.12 (2021): e14351. https://doi.org/10.15252/emmm.202114351

The article indicates that in liver cancer, YAP/TAZ maintains the protein stability and nuclear activity of ATF4, cooperatively upregulates the expression of SLC7A11, and inhibits sorafenib induced ferroptosis, thereby driving drug resistance. Targeting the YAP/TAZ-ATF4 axis may overcome drug resistance.

4. Zhang, Zeying, et al. "KPNB1-ATF4 induces BNIP3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells." Cellular & Molecular Biology Letters 29.1 (2024): 145. https://doi.org/10.1186/s11658-024-00664-9

The article indicates that in the differentiation of dental pulp stem cells, the KPNB1 protein recognizes ATF4 and helps it enter the nucleus. ATF4 then transcribs and activates BNIP3, inducing mitophagy and enhancing mitochondrial function, thereby promoting the differentiation of stem cells into odontoblasts. This axis provides a new target for pulp-dentin regeneration.

5. Chen, Chao, et al. "ATF4-dependent fructolysis fuels growth of glioblastoma multiforme." Nature communications 13.1 (2022): 6108. https://doi.org/10.1038/s41467-022-33859-9

The article indicates that in glioblastoma, when glucose is deficient, ATF4 is specifically activated and translated, thereby upregulating the expression of key fructose-decomposing proteins such as GLUT5 and ALDOB, which prompts cancer cells to turn to fructose for energy supply and promotes tumor growth. This pathway is a potential target.

Creative Biolabs: Atf4 Antibodies for Research

Creative Biolabs specializes in the production of high-quality Atf4 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom Atf4 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our Atf4 antibodies, custom preparations, or technical support, contact us at email.

Reference

Neill, Graham, and Glenn R. Masson. "A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response." Frontiers in Molecular Neuroscience 16 (2023): 1112253. https://doi.org/10.3389/fnmol.2023.1112253