Product Description
The ER responds to the accumulation of unfolded proteins in its lumen by activating intracellular signaling pathways, which is collectively termed the unfolded protein response (UPR). Three major branches of the UPR have been identified, including IRE1 (inositol requiring enzyme 1), PERK [double-stranded RNA-activated protein kinase (PKR)–like ER kinase], and ATF6 (activating transcription factor 6). The second branch of the UPR is mediated by PERK. Upon activation, PERK oligomerizes and phosphorylates itself and the ubiquitous translation initiation factor eIF2a, which inactivates eIF2 and inhibits mRNA translation. In this way, PERK helps reduce the flux of protein entering the ER to alleviate ER stress. In addition, eIF2a phosphorylation preferentially increases the translation of selective mRNAs that contain inhibitory upstream open reading frames (uORFs) within their 5’ untranslated region (UTR) that prevent translation in unstressed cells. The most studied of these genes is ATF4 (activating transcription factor 4). ATF4 belongs to the family of basic zipper-containing proteins. As a transcription factor, three conserved binding sites in the promoter regions of ATF4 target genes have been identified, including CRE site, amino acid response element (AARE) site, and nutrient-sensing response element-1 (NSRE-1) site. Two important target genes driven by ATF4 are CHOP (transcription factor C/EBP homologous protein) and GADD34 (growth arrest and DNA damage–inducible 34). CHOP is a transcription factor that controls genes encoding components involved in apoptosis. GADD34 encodes a PERK-inducible regulatory subunit of the protein phosphatase PP1C that counteracts PERK by dephosphorylating eIF2a. Lines of evidence have shown that ATF4 plays crucial roles in various physiological and pathological activities, such as ER stress, hematopoiesis, lens and skeletal development, hypoxia resistance, autophagy, amino acid deprivation, learning and memory formation, tumor development and neurodegeneration.
100μg
Verified Reactivity: Human, Mouse
Antibody Type: Monoclonal
Host Species: Rat
Immunogen: Partial human ATF4 (102-351 a.a.) expressed in E. coli.
Formulation: Phosphate-buffered solution, pH 7.2, containing 0.09% sodium azide.
Preparation: The antibody was purified by affinity chromatography.
Concentration: 0.5 mg/ml
Storage & Handling: The antibody solution should be stored undiluted between 2°C and 8°C.
Application: WB - Quality tested
Recommended Usage: Each lot of this antibody is quality control tested by Western blotting. For Western blotting, the suggested use of this reagent is 0.2 - 2.0 µg per ml. It is recommended that the reagent be titrated for optimal performance for each application.
Product Citations: Nigro I, et al. 2023. Int J Mol Sci. :25. PubMed Byles V, et al. 2021. Mol Metab. 53:101309. PubMed Moravcikova E, et al. 2017. Int J Cancer. 141:2050. PubMed Rinaldi R, et al. 2021. Cells. 10:. PubMed Wang LW, et al. 2019. Cell Metab. 30:539. PubMed Fresia D, et al. 2021. J Clin Med. 10:. PubMed
RRID: AB_2650719 (BioLegend Cat. No. 693901) AB_2650720 (BioLegend Cat. No. 693902)
Structure: 351 amino acids with a predicted molecular weight of 39 kD.
Distribution: Cytoplasm and nucleus.
Function: Transcriptional activator. Upregulates a UPR genes that function preferentially in amino acid import, glutathione biosynthesis, and resistance to oxidative stress.
Interaction: Binds DNA as a homodimer and as a heterodimer. Interacts with CEBPB, GABBR1 and GABBR2, FOXO1, SATB2, CEP290, NEK6, DAPK2, ZIPK/DAPK3, TXLNG, DDIT3/CHOP, FAM175B.
Biology Area: Cell Biology, Signal Transduction, Transcription Factors
Antigen References: 1. Walter P, Ron D. 2011. Science. 334:1081.2. Hetz C, et al. 2011. Physiol. Rev. 91:1219.3. Schroder M, Kaufman RJ. 2005. Annu. Rev. Biochem. 74:739.4. Mielnicki LM, Pruitt SC. 1991. Nucleic Acids Res. 19:6332.5. Siu F, et al. 2002. J. Biol. Chem. 277:24120.6. Masuoka HC, Townes TM. 2002. Blood. 99:736.7. Yang X, et al. 2004. Cell. 117(3):387-98.8. Ye J, Koumenis C. 2009. Curr. Mol. Med. 9:411.9. Milani M, et al. 2009. Cancer Res. 69:4415.10. Wei N, et al. 2015. Mol. Neurobiol. 52:1765.11. Rozpedek W, et al. 2016. Curr. Mol. Med. 16:533.
Gene ID: 468
UniProt: View information about ATF4 on UniProt.org
Clone: W16016A
Regulatory Status: RUO
Other Names: Activating transcription factor 4, Cyclic AMP-dependent transcription factor ATF-4, CREB-2, DNA-binding protein TAXREB67
Isotype: Rat IgG2a, κ
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Collaboration
Tony Tang
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