Nuclear respiratory factor 2 (NRF-2)

Nuclear respiratory factor 2 (NRF-2), also known as GA-binding protein (GABP), is a multimeric transcription factor consisting of an alpha (GABPA) and a beta (GABPB) subunit that plays a critical role in the coordination of nuclear and mitochondrial genomes (UniProt Q06546; PubMed: 26362534). It is essential for the expression of nuclear genes encoding mitochondrial proteins, including those involved in the electron transport chain and mitochondrial DNA replication (PubMed: 12615951). In clinical oncology, NRF-2 has emerged as a high-priority target due to its specific recruitment to mutant TERT promoters, where it drives telomerase reactivation in cancers such as glioblastoma and melanoma (PubMed: 25684077; Science, 2015). Beyond its role in cancer, GABP is vital for maintaining metabolic homeostasis and protecting against mitochondrial decay in aging and neurodegeneration (PubMed: 28416565). Therapeutic strategies currently under investigation focus on disrupting the GABPA-GABPB interaction or inhibiting GABP binding to oncogenic DNA sequences to selectively treat TERT-mutant tumors while minimizing systemic metabolic toxicity.

Other names

GA-binding proteinGABPGA-binding protein transcription factor subunit alphaGABPAE4TF1Transcription factor E4TF1-60

Modulation of GABP heterotetramer formation or inhibition of GABPA binding to ETS motifs in gene promoters, particularly at mutant TERT promoters in cancer cells.