Suppressor of Ty 5 homolog–RNA polymerase II protein–protein interface (SPT5–Pol II interface)

The Suppressor of Ty 5 homolog (SPT5)–RNA polymerase II (Pol II) protein–protein interface is a fundamental regulatory hub in the eukaryotic transcription cycle. SPT5, as a core component of the DRB-sensitivity inducing factor (DSIF) complex, binds directly to the Pol II clamp and protrusion domains to stabilize the transcription elongation complex (TEC) [1][2]. This interaction is essential for the transition of Pol II from promoter-proximal pausing to productive elongation, a step that is often rate-limiting for gene expression [3]. In many aggressive cancers, this interface is exploited to maintain high levels of oncogenic transcripts like MYC, while in HIV-1 infection, the viral Tat protein hijacks this interaction to facilitate rapid viral genome transcription [4][5]. Therapeutic targeting of this interface aims to disrupt the assembly of the elongation complex, offering a potentially more selective approach than broad kinase inhibition [6]. Experimental small molecules, such as SPI-1, have demonstrated the feasibility of directly inhibiting this protein-protein interaction to suppress oncogenic transcription in preclinical models [7]. Monitoring the phosphorylation status of SPT5 and the Pol II pausing index serves as a vital biomarker for evaluating the efficacy of drugs targeting this interface [8].

Other names

SPT5-Pol II interfaceDSIF-Pol II interactionSUPT5H-RNAP2 interfaceSPT5-RNAPII complexDRB-sensitivity inducing factor-RNA polymerase II interface

Disruption of the protein-protein interaction between the KOW domains of SPT5 and the RNA polymerase II clamp, preventing the formation of a stable elongation complex and inducing transcriptional pausing.