Fig. 1.

BRD4 protein degradation in the mouse brain by dBET1. A Schematic illustration of BRD4 PROTAC dBET1 mechanism-induced BRD4 protein degradation through the ubiquitin–proteasome system. With dBET1, E3 ligase recognizes, binds, and ubiquitinates BRD4 protein, making it available for subsequent proteasomal degradation. B Representative western blot depicts dBET1 (30 mg/kg; i.p. at 4 and 24 h) induces significant BRD4 degradation in the whole hemisphere and cerebral cortex of mice at 48 h after sham surgery. n = 4–5 per group, **P < 0.01, ***P < 0.001. C Representative western blot shows the BRD4 protein levels in the cerebral cortex of sham and stroke mice at 48 h after surgery. n = 5 per group. ***P < 0.001. D Representative western blot depicts dBET1 (30 mg/kg; i.p. at 4 and 24 h after stroke) reduces the protein level of BRD4 in the cerebral cortex under the condition of stroke by tMCAO. ***P < 0.001. Ub, ubiquitin; E1, E2, E3, ubiquitin-activating enzyme E1, E2, E3; BET, bromodomain and extra-terminal domain protein