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The NF-E2 DNA binding protein is composed of two subunits, p45 and MafK, and it regulates expression of globin genes in developing erythroid cells through interaction with Maf recognition elements (MAREs). A family of NF-E2 related proteins, which are collectively known as the Cap 'n' collar (CNC) family and include Nrf1 (also designated TCF11), Nrf2 and Nrf3, are bZIP transcription factors that heterodimerize with Maf proteins to bind MARE sequences. The Nrf proteins also bind the antioxidant response element (ARE) and are implicated in the regulation of detoxification enzymes and the oxidative stress response. They do so by heterodimerizing with Jun family members (c-Jun, JunB and JunD) to activate gene expression, specifically the detoxifying enzyme, NQO1. Nrf2 is widely expressed and is thought to translocate to the nucleus after treatment with xenobiotics and antioxidants, which stimulate its release from a repressor protein Keap1. Nrf3 is highly expressed in placenta, B cells and monocytes.
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