NFE2L2

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NFE2L2 (Nuclear factor erythroid 2-related factor 2) is a transcription factor encoded by the NFE2L2 gene in humans. It plays a crucial role in the regulation of the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation.

Function

NFE2L2 is a member of the Cap 'n' Collar (CNC) family of transcription factors. It is primarily involved in the cellular response to oxidative stress. Under normal conditions, NFE2L2 is bound by KEAP1 (Kelch-like ECH-associated protein 1) in the cytoplasm, which targets it for ubiquitination and subsequent degradation by the proteasome. However, under oxidative stress, NFE2L2 is released from KEAP1, translocates to the nucleus, and binds to the Antioxidant Response Element (ARE) in the promoter regions of target genes. This binding initiates the transcription of various cytoprotective genes, including those involved in glutathione synthesis, NADPH regeneration, and the detoxification of reactive oxygen species (ROS).

Clinical Significance

Mutations and dysregulation of NFE2L2 have been implicated in several diseases, including cancer, neurodegenerative diseases, and chronic obstructive pulmonary disease (COPD). Overexpression of NFE2L2 has been observed in various types of cancer, where it contributes to the survival and proliferation of cancer cells by enhancing their antioxidant capacity. Conversely, loss of NFE2L2 function can lead to increased susceptibility to oxidative stress and related pathologies.

Interactions

NFE2L2 interacts with several proteins, including:

• KEAP1: Regulates the stability and activity of NFE2L2.
• MafG: Forms heterodimers with NFE2L2 to bind to ARE.
• CUL3: Part of the E3 ubiquitin ligase complex that targets NFE2L2 for degradation.

Research

Ongoing research is focused on understanding the precise mechanisms of NFE2L2 regulation and its role in disease. Therapeutic strategies aimed at modulating NFE2L2 activity are being explored for the treatment of diseases associated with oxidative stress.

See Also

• Oxidative stress
• Transcription factor
• KEAP1
• Antioxidant Response Element (ARE)

External Links

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