Nuclear Factor Erythroid-2 Like 1 (NFE2L1): Structure, function and regulation

• Nrf1is a CNC-bZIP transcription factor.
• Nrf1 regulates expression of genes involved in cellular stress response.
• Nrf1 is critical for maintaining proteostasis.
• Nrf1 expression is controlled by its protein stability.
• Knockout mouse studies suggest the importance of Nrf1 in cancer, neurodegenerative and metabolic disorders.

Nrf1 (also referred to as NFE2L1) is a member of the CNC-bZIP family of transcription factors that are characterized by a highly conserved CNC-domain, and a basic-leucine zipper domain required for dimerization and DNA binding. Nrf1 is ubiquitously expressed across tissue and cell types as various isoforms, and is induced by stress signals from a broad spectrum of stimuli. Evidence indicates that Nrf1 plays an important role in regulating a range of cellular functions including oxidative stress response, differentiation, inflammatory response, metabolism, and maintaining proteostasis. Thus, Nrf1 has been implicated in the pathogenesis of various disease processes including cancer development, and degenerative and metabolic disorders. This review summarizes our current understanding of Nrf1 and the molecular mechanism underlying its regulation and action in different cellular functions.