Transcription factor IIB-related factor 2–TATA-box binding protein interface (BRF2–TBP interface)

The BRF2–TBP protein-protein interface is a critical structural junction within the RNA polymerase III (Pol III) transcription initiation complex TFIIIB. BRF2 (Transcription factor IIB-related factor 2) is a specialized subunit that recruits Pol III to type 3 promoters, such as those for U6 small nuclear RNA and other genes involved in the oxidative stress response. In many cancers, particularly lung squamous cell carcinoma, BRF2 is frequently overexpressed or amplified, acting as an oncogene by driving the production of small RNAs that support rapid cell proliferation and metabolic adaptation. The interaction between the C-terminal domain of BRF2 and the TATA-box binding protein (TBP) is essential for the stable assembly of the transcription machinery on DNA. Targeting this specific protein-protein interface offers a therapeutic strategy to selectively inhibit Pol III-driven transcription in cancer cells while potentially sparing the more ubiquitous BRF1-dependent Pol III transcription. Small molecule inhibitors designed to disrupt this interface are currently being explored as precision oncology agents to suppress the hypertrophic transcription program characteristic of malignant cells.

Other names

BRF2-TBP complexTFIIIB subunit BRF2-TBP interactionBRF2-TBP protein-protein interaction

Disruption of the protein-protein interaction between BRF2 and TBP prevents the assembly of the TFIIIB complex, thereby inhibiting the recruitment of RNA polymerase III to specific promoter regions and suppressing the transcription of small non-coding RNAs required for high metabolic demands in cancer cells.