NFE2L2 Protein, Mouse (His)

NF2L2 is a transcription factor that plays a key role in the response to oxidative stress by binding to antioxidant response (ARE) elements in the promoter regions of cytoprotective genes, such as phase 2 detoxifying enzymes, promoting their expression to neutralize reactive electrophiles. Under normal conditions, NF2L2 is ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. During oxidative stress, electrophile metabolites inhibit the BCR(KEAP1) complex, leading to nuclear accumulation of NF2L2/NRF2, heterodimerization with small Maf proteins, and binding to ARE elements of cytoprotective target genes. The NF2L2/NRF2 pathway is also activated during selective autophagy, where autophagy promotes KEAP1-SQSTM1/p62 interaction, inactivating the BCR(KEAP1) complex and enhancing NF2L2/NRF2 nuclear accumulation and cytoprotective gene expression. Additionally, this pathway is activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival after endoplasmic reticulum stress. NF2L2 may also mediate enhancer activity of hypersensitive site 2 in the β-globin locus control region to activate β-globin cluster genes (by similar). It is crucial in regulating innate immunity, maintaining redox homeostasis, and restraining pro-inflammatory signaling pathways (e.g., MyD88-dependent/-independent and TNF-alpha) during sepsis. NF2L2 suppresses macrophage inflammatory responses by blocking pro-inflammatory cytokine transcription and IL6 induction, inhibiting RNA Pol II recruitment independently of the Nrf2-binding motif or reactive oxygen species levels. It also represses antiviral cytosolic DNA sensing by suppressing STING1 expression, reducing responsiveness to STING1 agonists while increasing susceptibility to DNA virus infections (by similar).