NFE2L2

NFE2L2, nuclear factor (erythroid-derived 2)-related factor 2, alias NRF2, NFE2L2. it is a transcription factor, encoded by its own genes in human cells, that plays a key role in cellular defense against oxidative stress and in the removal of deleterious substances. the mechanism of action of NFE2L2 involves multiple dimensions including post-translational modifications, protein interactions and epigenetic regulation. Under normal physiological conditions, NFE2L2 binds to KEAP1 and promotes its degradation via the ubiquitin-proteasome pathway, maintaining NFE2L2 expression at a low level. When cells are exposed to oxidative stress or electrophilic reagents, NFE2L2 is translocated from the cytoplasm to the nucleus, where it binds to antioxidant response elements (AREs) and activates the transcription of antioxidant-related genes.

The biological significance of NFE2L2 is very broad, and it is involved in the regulation of the metabolic process of aflatoxin catabolism, the positive regulation of macromolecular metabolic processes, and the regulation of cell migration.The function of NFE2L2 Abnormalities are associated with a variety of diseases, including diabetic retinopathy, cirrhosis, middle cerebral artery infarction, and nonalcoholic fatty liver disease. In addition, direct human homozygotes for NFE2L2 have been associated with Alzheimer's disease, cataracts, hepatocellular carcinoma, macular degeneration, tuberculosis, and other diseases. In cancer, the NFE2L2-KEAP1 signaling pathway is frequently hijacked, especially in non-small cell lung cancer, where activation of NFE2L2 can lead to cancer cells escaping various anti-tumor therapies and promote disease progression and metastasis. Therefore, NFE2L2 is an important target in cellular oxidative stress response and disease therapy.