Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.14.99.3 (
heme oxygenase
)
4,196
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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. We integrated the RNA-Seq results with DNA-binding sites of
BRD4
generated by chromatin immunoprecipitations, correlated these with gene expressions from human prostate cancers and identified 21 top
BRD4
candidate genes among which the oxidative stress pathway genes KEAP1, SESN3 and HDAC6 are represented. Knock down of
BRD4
or treatment with the
BRD4
inhibitor JQ1 resulted in decreased reactive oxygen species (ROS) production and increased cell viability under H2O2 exposure. Consistently, a deregulation of
BRD4
diminished the KEAP1/NRF2 axis and led to a disturbed regulation of the inducible
heme oxygenase
1 (HMOX1). Without exogenous stress induction, we also found
BRD4
directly targeting the HMOX1 promoter over the SP1-binding sites. Our findings provide insight into the transcriptional regulatory network of
BRD4
and highlight
BRD4
as signal transducer of the cellular response to oxidative stress.
...
PMID:The bromodomain protein BRD4 regulates the KEAP1/NRF2-dependent oxidative stress response. 2476 52
