Skip to main content

Main menu

  • Home
  • About the Journal
    • General Information
    • Scope
    • Editorial Board
    • Impact & Metrics
    • Benefits of Publishing
    • Advertising/Sponsorship
    • About the Biochemical Society
  • Current Issue
  • For Authors
    • Submit Your Paper
    • Submission Guidelines
    • Editorial Policy
    • Open Access Policy
    • Rights and Permissions
    • Biochemical Society Member Benefits
  • For Librarians
    • Subscriptions and Pricing
    • Check Your Usage
    • Terms and Conditions
      • Biochemical Journal- Terms and Conditions of Usage
    • Open Access Policy
    • FAQs for Librarians
    • Register for Free Trial
  • For Readers
    • Subscribe
    • Rights and Permissions
    • Biochemical Society Member Benefits
    • Journal Access for Biochemical Society Members
    • Request a Free Trial
  • Collections
    • Article Collections
    • Classic Articles
  • Help
    • Technical Support
    • Contact Us
  • Other Publications
    • NEW: Emerging Topics in Life Sciences
    • NEW: Neuronal Signaling
    • Clinical Science
    • Biochemical Journal
    • Biochemical Society Transactions
    • Bioscience Reports
    • Essays in Biochemistry
    • Biochemical Society Symposia
    • Cell Signalling Biology
    • Glossary of Biochemistry and Molecular Biology
    • The Biochemist
    • Biochemical Society

User menu

  • Log-in
  • Subscribe
  • Contact Us

Search

  • Advanced search
  • Other Publications
    • NEW: Emerging Topics in Life Sciences
    • NEW: Neuronal Signaling
    • Clinical Science
    • Biochemical Journal
    • Biochemical Society Transactions
    • Bioscience Reports
    • Essays in Biochemistry
    • Biochemical Society Symposia
    • Cell Signalling Biology
    • Glossary of Biochemistry and Molecular Biology
    • The Biochemist
    • Biochemical Society

Log-in

Sign-up for alerts  
  • My Cart
Biochemical Journal
Browse Archive
Advanced Search
  • Home
  • About the Journal
    • General Information
    • Scope
    • Editorial Board
    • Impact & Metrics
    • Benefits of Publishing
    • Advertising/Sponsorship
    • About the Biochemical Society
  • Current Issue
  • For Authors
    • Submit Your Paper
    • Submission Guidelines
    • Editorial Policy
    • Open Access Policy
    • Rights and Permissions
    • Biochemical Society Member Benefits
  • For Librarians
    • Subscriptions and Pricing
    • Check Your Usage
    • Terms and Conditions
    • Open Access Policy
    • FAQs for Librarians
    • Register for Free Trial
  • For Readers
    • Subscribe
    • Rights and Permissions
    • Biochemical Society Member Benefits
    • Journal Access for Biochemical Society Members
    • Request a Free Trial
  • Collections
    • Article Collections
    • Classic Articles
  • Help
    • Technical Support
    • Contact Us

Review article

SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR

Jenny Wong, Carmel M. Quinn, Andrew J. Brown
Biochemical Journal Nov 28, 2006, 400 (3) 485-491; DOI: 10.1042/BJ20060914
Jenny Wong
School of Biotechnology and Biomolecular Sciences, Biosciences Building D26, The University of New South Wales, Sydney, NSW 2052, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • View author's works on this site
Carmel M. Quinn
Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaCentre for Vascular Research, Department of Haematology, Prince of Wales Hospital, Sydney, NSW 2031, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • View author's works on this site
Andrew J. Brown
School of Biotechnology and Biomolecular Sciences, Biosciences Building D26, The University of New South Wales, Sydney, NSW 2052, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • View author's works on this site
  • For correspondence: aj.brown@unsw.edu.au
  • Article
  • Figures
  • Info & Metrics
  • Supplementary Data
  • PDF
Loading

Abstract

Cholesterol accumulation and removal are regulated by two different transcription factors. SREBP-2 (sterol-regulatory-element-binding protein-2) is best known to up-regulate genes involved in cholesterol biosynthesis and uptake, whereas LXR (liver X receptor) is best known for up-regulating cholesterol efflux genes. An important cholesterol efflux gene that is regulated by LXR is the ATP-binding cassette transporter, ABCA1 (ATP-binding cassette transporter-A1). We have previously shown that statin treatment down-regulated ABCA1 expression in human macrophages, probably by inhibiting synthesis of the LXR ligand 24(S),25-epoxycholesterol. However, it was subsequently reported that ABCA1 expression is down-regulated by SREBP-2 through binding of SREBP-2 to an E-box element in ABCA1's proximal promoter. As statin treatment induces SREBP-2 activation, this may provide an alternative explanation for the statin-mediated down-regulation of ABCA1. In the present study, we employed a set of CHO (Chinese-hamster ovary) mutant cell lines to investigate the role of SREBP-2 in the regulation of ABCA1. We observed increased ABCA1 mRNA levels in SREBP-2-overexpressing cells and decreased levels in cells lacking a functional SREBP-2 pathway, which were restored when the SREBP-2 pathway was reinstated. Moreover, ABCA1 gene expression was positively associated with synthesis of 24(S),25-epoxycholesterol in these cell lines. In studies using a human ABCA1 promoter reporter assay, mutation of the E-box motif had a similar response as the wild-type construct to either statin treatment or addition of 24(S),25-epoxycholesterol. By contrast, these responses were completely ablated when the DR4 element to which LXR binds was mutated. These results support the idea that 24(S),25-epoxycholesterol and statin treatment influence ABCA1 transcription via supply of an LXR ligand and not through an SREBP-2/E-box-related mechanism. In addition, our results indicate a critical role of SREBP-2 as a positive regulator of ABCA1 gene expression by enabling the generation of oxysterol ligands for LXR.

  • ATP-binding-cassette transporter-A1 (ABCA1)
  • E-box
  • 24(S)
  • 25-epoxycholesterol
  • liver X receptor (LXR)
  • statin
  • sterol-regulatory-element-binding protein 2 (SREBP-2)

Abbreviations: ABCA1, ATP-binding cassette transporter-A1; CHO, cell, Chinese-hamster ovary cell; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; LDL, low-density lipoprotein; LDL-R, LDL receptor; LPDS, lipoprotein-deficient serum; LXR, liver X receptor; NBS, newborn calf serum; PBGD, porphobilinogen deaminase; RT, reverse transcriptase; QRT–PCR, quantitative (‘real-time’) RT–PCR; SREBP, sterol-regulatory-element-binding protein; SCAP, SREBP cleavage activating protein; SRE, sterol-regulatory element

  • The Biochemical Society, London
View Full Text

Log in using your username and password

Enter your Biochemical Journal username.
Enter the password that accompanies your username.
Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
Previous ArticleNext Article
Back to top

 

 

December 2006

Volume: 400 Issue: 3

Biochemical Journal: 400 (3)
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Ed Board (PDF)
  • Front Matter (PDF)

Actions

Email

Thank you for your interest in spreading the word about Biochemical Journal.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR
(Your Name) has forwarded a page to you from Biochemical Journal
(Your Name) thought you would like to see this page from the Biochemical Journal web site.
Share
SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR
Jenny Wong, Carmel M. Quinn, Andrew J. Brown
Biochemical Journal Dec 2006, 400 (3) 485-491; DOI: 10.1042/BJ20060914
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Facebook logo Mendeley logo
Citation Tools
SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR
Jenny Wong, Carmel M. Quinn, Andrew J. Brown
Biochemical Journal Dec 2006, 400 (3) 485-491; DOI: 10.1042/BJ20060914

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print
Alerts

Please log in to add an alert for this article.

Request Permissions
Save to my folders

View Full PDF

 Open in Utopia Docs
  • Tweet Widget
  • Facebook Like

Jump To

  • Article
    • Abstract
    • INTRODUCTION
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Acknowledgments
    • References
  • Figures
  • Info & Metrics
  • Supplementary Data
  • PDF

Keywords

ATP-binding-cassette transporter-A1 (ABCA1)
E-box
24(S)
25-epoxycholesterol
liver X receptor (LXR)
statin
sterol-regulatory-element-binding protein 2 (SREBP-2)

Related Articles

Cited By...

Subjects

  • Gene
  • Portland Press Homepage
  • Publish With Us
  • Advertising
  • Technical Support
  • Biochemical Journal
  • Clinical Science
  • Essays in Biochemistry
  • Emerging Topics in Life Sciences
  • Biochemical Society Transactions
  • Neuronal Signaling
  • Bioscience Reports
  • Cell Signalling Biology
  • Biochemical Society Symposia

Portland Press Limited
Charles Darwin House
12 Roger Street
London WC1N 2JU
Tel: +44(0) 20 7685 2410
Fax: +44(0) 20 7685 2469
Email: editorial@portlandpress.com

The Biochemical Society