Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.

Transcription is regulated by specific transcription factors that mediate signaling in response to extrinsic and intrinsic stimuli such as nutrients, hormones, and oxidative stresses. Many transcription factors are grouped based on their highly conserved DNA binding domains. Consequently, transcription factors within the same family often exhibit functional redundancy and compensation. NRF2 (NFE2L2) and NRF1 (NFE2L1) belong to the CNC family transcription factors, which are responsible for various stress responses. Although their DNA binding properties are strikingly similar, NRF2 and NRF1 are recognized to play distinct roles in a cell by mediating responses to oxidative stress and proteotoxic stress, respectively. In this review, we here overview the distinct and shared roles of NRF2 and NRF1 in the transcriptional regulation of target genes, with a particular focus on the nuclear protein binding partners associated with each factor.