A Novel Function of Novobiocin: Disrupting the Interaction of HIF 1α and p300/CBP through Direct Binding to the HIF1α C-Terminal Activation Domain
Figure 7
Potential therapeutic model of novobiocin on cancer.
Under hypoxia, HIF1α dimerises with HIF1β, recruits transcriptional coactivator p300/CBP, and binds to the HRE, thereby leading to activation of hypoxically regulated genes such as VEGF and CA9 (upper panel). Novobiocin directly binds to HIF1α CTAD, inhibits the recruitment of transcriptional co-activator p300/CBP, leading to reduction of hypoxically regulated genes. Ultimately, this suppresses tumor well growth (lower panel).