Abstract
Bromodomain and extraterminal domain protein 2 (BRD2), a member of the bromodomain and extraterminal domain (BET) protein family, is a crucial epigenetic regulator with significant function in various diseases and cellular processes. The central function of BRD2 is modulating gene transcription by binding to acetylated lysine residues on histones and transcription factors. This review highlights key findings on BRD2 in recent years, emphasizing its roles in maintaining genomic stability, influencing chromatin spatial organization, and participating in transcriptional regulation. BRD2’s diverse functions are underscored by its involvement in diseases such as malignant tumors, neurologic disorders, inflammatory conditions, metabolic diseases, and virus infection. Notably, the potential role of BRD2 as a diagnostic marker and therapeutic target is discussed in the context of various diseases. Although pan inhibitors targeting the BET family have shown promise in preclinical studies, a critical need exists for the development of highly selective BRD2 inhibitors. In conclusion, this review offers insights into the multifaceted nature of BRD2 and calls for continued research to unravel its intricate mechanisms and harness its therapeutic potential.
SIGNIFICANCE STATEMENT BRD2 is involved in the occurrence and development of diseases through maintaining genomic stability, influencing chromatin spatial organization, and participating in transcriptional regulation. Targeting BRD2 through protein degradation–targeting complexes technology is emerging as a promising therapeutic approach for malignant cancer and inflammatory diseases.
Footnotes
- Received December 4, 2023.
- Accepted March 25, 2024.
This work was supported by National Natural Science Foundation of China (82073384, 82272815, and 82230090), Shanghai Committee of Science and Technology (21DZ2292000), The Double Hundred Plan of Shanghai Jiao Tong University School of Medicine (20191812), and The Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212301) (to W.C. and X.W.).
The authors declare that they have no competing interests.
- Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics
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