Purified anti-ATF4 Antibody anti-ATF4 - W16016A,BioLegend,693902

The ER responds to theaccumulationofunfolded proteins in its lumenby activating intracellularsignalingpathways,which iscollectively 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.