Mar 29, 2022 · Using molecular and pharmacological approaches, we then discovered that BRD4 can directly bind to the promoter of KEAP1 to activate its transcription and down-regulate the stability of Nrf2 which in turn transcriptionally suppresses glucose-6-phosphate dehydrogenase (G6PD) in small cell lung cancer (SCLC), a highly proliferative and aggressive ...

Apr 24, 2014 · We have found the KEAP1/NRF2 stress response to be regulated by bromodomain-containing protein 4 (BRD4).

We identified BRD4 as a potential factor positively modulating KEAP1 expression at the transcriptional level in lung cancer. Using small cell lung cancer (SCLC) as a model, we further found that BRD4 binds to the promoter region of KEAP1 …

Apr 24, 2014 · The epigenetic sensor BRD4 (bromodomain protein 4) is a potent target for anti-cancer therapies. To study the transcriptional impact of BRD4 in cancer, we generated an expression signature of BRD4 knockdown cells and found oxidative stress response genes significantly enriched.

BRD4 inhibition promoted Nrf2 nuclear translocation and upregulated the transcriptional activity of Nrf2/antioxidant response element (ARE). However, Nrf2 silencing partially reversed BRD4-inhibition-mediated protection against HG-induced podocyte injury.

Jun 15, 2020 · Using small molecule inhibitor JQ1 targeting Bromodomain and extra-terminal family proteins, we showed restrained iNOS-dependent nitric oxide (NO) production correlated with abolished Brd4...

BRD4, KEAP1, NRF2 and HMOX1 in three prostate cancer cell lines (DU-145, LNCAP and PC3), we found a significant upregulation of BRD4 and KEAP1 and a downregulation of NRF2 in all cell lines ...

Feb 2, 2018 · Brd4 appears to activate autophagy directly through modulating the expression of autophagy-associated genes and indirectly through increasing ROS by KEAP1 activation and the subequent downregulation of the Nrf2 antioxidant pathway. Brd4 is a validated drug target in leukemia and Brd4 chromatin occupancy in AML correlates with the ...

Under baseline conditions, BRD4 constitutively binds to promoter sites of genes regulated by the transcription factor NRF2 [18, 46], and plays a role as both a gene expression inhibitor as well as activator, a mechanism that is cell-type dependent .

Apr 24, 2014 · BRD4 (pcDNA-BRD4-FL), NRF2 (pTL-FlagC-NRF2) expressing constructs or empty vectors (EV) were co-transfected with a luciferase reporter plasmid carrying the HMOX1 promoter either with (E1-HMOX1-WT) or without (HMOX1-WT) the first enhancer region of …