English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The bromodomain protein BRD4 regulates the KEAP1/NRF2 dependent oxidative stress response

Hussong, M., Börno, S. T., Kerick, M., Wunderlich, A., Franz, A., Sültmann, H., et al. (2014). The bromodomain protein BRD4 regulates the KEAP1/NRF2 dependent oxidative stress response. Cell Death and Disease, 2014(5): e1195. doi:10.1038/cddis.2014.157.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-A6BC-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-77D3-6
Genre: Journal Article

Files

show Files
hide Files
:
Hussong.pdf (Publisher version), 2MB
Name:
Hussong.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2014 Macmillan Publishers Limited
License:
-

Locators

show

Creators

show
hide
 Creators:
Hussong, M.1, Author              
Börno, S. T.2, Author              
Kerick, M.2, Author              
Wunderlich, A.1, Author              
Franz, A., Author
Sültmann, H., Author
Timmermann, B.2, Author              
Lehrach, H.3, Author              
Hirsch-Kauffmann, M., Author
Schweiger, M. R.1, Author              
Affiliations:
1Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479649              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
3Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

Content

show
hide
Free keywords: oxidative stress; bromodomain protein BRD4; heme oxygenase 1
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2014-04-24
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/cddis.2014.157
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Cell Death and Disease
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 2014 (5) Sequence Number: e1195 Start / End Page: - Identifier: -