A natural product targets BRD4 to inhibit phase separation and gene transcription
Cong Wang, Huasong Lu, Xiangzhong Liu, Xiang Gao, Wenjing Tian, Haifeng Chen, Yuhua Xue, Qiang Zhou
Abstract
Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.
Topics & Concepts
BromodomainBRD4Transcription (linguistics)EnhancerTranscription factorNatural productHistoneGeneBET inhibitorChemistryComputational biologyCell biologyBiologyBiochemistryPhilosophyLinguisticsProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysMultiple Myeloma Research and Treatments