The Big BRD Wolf
As research investigating the interplay between BRD and histone proteins has progressed it is apparent that there is a significant relationship between the BRDs and the number of cellular conditions with implications for human health. For example, because of the relationship of BRD to cellular division, it logically follows that aberrant BRD function could result in malignant cell growth and cancer. BRD proteins have been associated with certain types of cancer, such as breast cancer, as a result of their control of the gene encoding cyclin D11. Though it has not been shown conclusively, it has been postulated that inhibition of these BRD proteins may help reduce increased cell division seen in cyclin D1-associated cancers. Furthermore, thymic carcinoma has been observed in a small number of patients whose BRD3 and BRD4 genes are mutated2. In addition, it is thought that inhibition of BRD3 and BRD4 by other cellular proteins may play a role in Burkitt's lymphoma and leukemia3,4.
Despite its importance toward our understanding and treatment of cancer, recent research has focused more on the relationship of BRD proteins to human immunodeficiency virus (HIV)-infected patients. When HIV infects an individual, its DNA is released inside the patient’s cells and integrates itself into the host DNA. This integration allows the virus to avoid the immune response. This avoidance persists until an unknown signal activates HIV from this latent state and new viral particles are made. BRD4 and the HIV protein Tat both interact with regions of DNA associated with HIV replication5. If BRD4 could be inhibited, it may allow for Tat to reactivate viral replication and make elimination of the virus more plausible. Interference with BRD2 has a similar effect as its inhibition can also promote the reactivation of HIV from its latent state6.
As knowledge about the functions of BRD2, BRD3, and BRD4 evolves, the need for tools to study, manipulate, and differentiate these crucial transcription factors will become increasingly significant to both general human health and to understanding the mechanics of cell-cycle control. Bethyl's intent for its validated BRD antibodies is to facilitate further discoveries that advance our understanding of BRD protein function and ultimately improving the lives of patients.