Description:

ER stress (UPR) response is governed by three transmembrane sensors: PERK, IRE1 and ATF6. These stress sensors control a complex ER-to-nucleus signaling pathway that transmits information across the ER membrane to an extensive gene-expression program. Two major transcription factors for UPR are ATF4 and ATF6. Both ATF4 and ATF6 belong to a basic leucine zipper ATF/CREB family, but have distinct functions UPR. ATF6 is a type II transmembrane ER protein that is activated by proteolytic cleavage. Active ATF6 translocates to the nucleus where it forms active homodimers or dimerizes with NF-Y and XBP1s and binds to promoter regions containing ATF/cAMP response elements (CREs) and/or ER Stress Elements (ERSE). ATF4 belongs to PERK-eIF2-ATF4 axis and regulates the expression of genes involved in amino acid biosynthesis and transport functions, antioxidant stress responses, and apoptosis. ATF4 induces both pro-survival (early) and pro-apoptotic (late) transcriptional programs. Prolonged or extreme ER stress uses ATF4 to upregulate proapoptotic protein C/EBP homologous protein (CHOP). To distinguish the function of ATF4 and ATF6 in ER stress, Signosis has developed ATF4 /ATF6 ELISA kit for detecting and comparing ATF4 and ATF6 DNA binding activities for human, mouse and rat samples.