Zinc-finger transcription factor (ZNF)

Zinc-finger transcription factors (ZNFs) constitute the largest family of DNA-binding proteins in humans, characterized by small, functional motifs stabilized by the coordination of one or more zinc ions (UniProt, 2023). These proteins are essential regulators of gene expression, binding to specific DNA sequences to modulate the transcription of genes involved in cell growth, differentiation, and development (NIH, 2022). Beyond DNA binding, some ZNFs also mediate RNA binding and protein-protein interactions, making them central hubs in cellular signaling networks. In clinical contexts, ZNFs are frequently implicated in oncogenesis, where mutations or expression changes drive tumor progression, as well as in various hereditary syndromes (PubMed, 2021). Although they were long deemed difficult to target with small molecules, the advent of molecular glues like lenalidomide has demonstrated that specific ZNFs can be targeted for proteasomal degradation (Nature, 2014). Furthermore, engineered zinc finger nucleases (ZFNs) represent a significant advancement in gene editing, allowing for precise therapeutic modifications of the genome (Sangamo, 2023).

Other names

Zinc finger proteinZNFC2H2-type zinc finger proteinZinc finger-containing transcription factor

Targeted protein degradation via molecular glues; competitive inhibition of DNA binding; site-specific genome editing via zinc finger nucleases (ZFNs).