Nucleolar transcription factor 1 (UBTF) (UBTF)

Nucleolar transcription factor 1 (UBTF), also known as Upstream Binding Factor (UBF), is a member of the HMG-box DNA-binding protein family and plays a central role in the regulation of ribosomal RNA (rRNA) transcription by RNA polymerase I (UniProt Consortium, 2024). It functions by binding to the ribosomal DNA (rDNA) promoter and enhancer elements, facilitating the recruitment of the transcription machinery and maintaining an open chromatin state in the nucleolus (Sanij et al., 2017). UBF is particularly significant in the context of platinum-based chemotherapy, as it exhibits a high affinity for DNA adducts formed by cisplatin (Treiber et al., 1992). This interaction leads to the sequestration of UBF from its functional sites on rDNA, effectively "hijacking" the transcription factor and causing a shutdown of ribosome biogenesis, which triggers p53-independent apoptosis in cancer cells (Zhai et al., 2002). Beyond its role in cancer, UBF is essential for cellular homeostasis, and mutations in the UBTF gene have been linked to progressive neurodegenerative disorders, highlighting its critical role in neuronal health (Sedlacek et al., 2019). Consequently, UBF is considered both a mediator of cisplatin's cytotoxicity and a potential target for novel small molecules designed to disrupt Pol I transcription in hyperproliferative cells.

Other names

Upstream binding factorUBFUBF1UBF2NOR-90

Cisplatin-DNA adducts act as decoys for UBF, sequestering it from the rDNA promoter and thereby inhibiting RNA polymerase I transcription, which triggers nucleolar stress and apoptosis (Treiber et al., 1992; Zhai et al., 2002).