Nuclear factor erythroid 2-like factor 3 (NFE2L3)

Nuclear factor erythroid 2-like factor 3 (NFE2L3, also known as NRF3) is a member of the Cap 'n' Collar (CNC) basic leucine zipper (bZIP) transcription factor family, encoded by the *Nfe2l3* gene, located at chromosome 7p15-p14 in humans. NFE2L3 primarily resides in the endoplasmic reticulum membrane, from which it can be cleaved and translocated to the nucleus upon cellular or oxidative stress, where it forms heterodimers with small MAF transcription factors to regulate gene expression of targets involved in stress response, detoxification, cell cycle, and differentiation. NFE2L3 supports cellular homeostasis by modulating antioxidant enzymes and proteasome activity and has been implicated in the regulation of tumor growth and progression in multiple cancers. It exhibits isoform-specific subcellular localization and is tightly regulated via post-translational modifications such as glycosylation, ubiquitination, and phosphorylation, notably by GSK3B and E3 ligases like FBW7, HRD1/VCP, and β-TRCP. NFE2L3 is of significant research interest due to its roles in oncogenesis; abnormally high expression correlates with poor prognosis or malignancy in multiple tumor types, positioning it as a potential biomarker and therapeutic target.

Other names

Nuclear factor erythroid 2-related factor 3NRF3Nrf3NF-E2-related factor 3NFE2-related factor 3nuclear factor, erythroid derived 2, like 3nuclear factor, erythroid 2 like 3nuclear factor-erythroid 2 p45-related factor 3

No established mechanism for direct small-molecule targeting; NFE2L3 acts via transcription regulation and post-translational modification.