BET‐ting on Nrf2: How Nrf2 Signaling can Influence the Therapeutic Activities of BET Protein Inhibitors. (30th March 2018)

• Record Type: Journal Article
• Authors: Chatterjee, Nirmalya; Bohmann, Dirk
• Is Part Of: BioEssays. Volume 40:Number 5(2018:May)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-03-30
• Subjects: AML -- BET proteins -- cancer -- COPD -- inflammation -- Nrf2 signaling -- oxidative stress; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.201800007
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract : BET proteins such as Brd3 and Brd4 are chromatin‐associated factors, which control gene expression programs that promote inflammation and cancer. The Nrf2 transcription factor is a master regulator of genes that protect the organism against xenobiotic attack and oxidative stress. Nrf2 has demonstrated anti‐inflammatory activity and can support cancer cell malignancy. This review describes the discovery, mechanism and biomedical implications of the regulatory interplay between Nrf2 and BET proteins. Both Nrf2 and BET proteins are established drug targets. Small molecules that either activate or suppress these proteins are currently tested in clinical trials. The crosstalk between Nrf2 and BET proteins may have important, and until now overlooked, implications for the therapeutic effects of these drugs. Based on the information covered in this review, it should be possible to design combinatorial treatment strategies for cancer and inflammatory diseases, which may improve the efficacy of targeting a Nrf2 or BET proteins individually. Abstract : BET proteins inhibit Nrf2 independently of Keap1. They promote cancer and inflammation. Nrf2 prevents inflammation but promotes cancer cell survival. Combinations of BET and Keap1 inhibitors synergistically activate Nrf2 and might be more effective in treating inflammation. Conversely, combining BET and Nrf2 inhibitors might be a promising cancer treatment strategy.