NDLI: Direct Interaction of Nuclear Liver X Receptor-β with ABCA1 Modulates Cholesterol Efflux* S⃞

Content Provider	PubMed Central
Author	Masako, Hozoji Munehira, Youichi Ikeda, Yuika Makishima, Makoto Matsuo, Michinori Kioka, Noriyuki Ueda, Kazumitsu
Abstract	Cholesterol is an essential component of eukaryotic cells; at the same time, however, hyperaccumulation of cholesterol is harmful. Therefore, the ABCA1 gene, the product of which mediates secretion of cholesterol, is highly regulated at both the transcriptional and post-transcriptional levels. The transcription of ABCA1 is regulated by intracellular oxysterol concentration via the nuclear liver X receptor (LXR)/retinoid X receptor (RXR); once synthesized, ABCA1 protein turns over rapidly with a half-life of 1–2 h. Here, we show that the LXRβ/RXR complex binds directly to ABCA1 on the plasma membrane of macrophages and modulates cholesterol secretion. When cholesterol does not accumulate, ABCA1-LXRβ/RXR localizes on the plasma membrane, but is inert. When cholesterol accumulates, oxysterols bind to LXRβ, and the LXRβ/RXR complex dissociates from ABCA1, restoring ABCA1 activity and allowing apoA-I-dependent cholesterol secretion. LXRβ can exert an immediate post-translational response, as well as a rather slow transcriptional response, to changes in cellular cholesterol accumulation. Thus, we provide the first demonstration that protein-protein interaction suppresses ABCA1 function. Furthermore, we show that LXRβ is involved in both the transcriptional and post-transcriptional regulation of the ABCA1 transporter.
Related Links	http://dx.doi.org/10.1074/jbc.m804599200
Ending Page	30063
Page Count	7
Starting Page	30057
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	44
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2008-10-31
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Direct Interaction of Nuclear Liver X Receptor-β with ABCA1 Modulates Cholesterol Efflux

Direct interaction of nuclear liver X receptor-beta with ABCA1 modulates cholesterol efflux.

Inhibition of ERK1/2 and Activation of Liver X Receptor Synergistically Induce Macrophage ABCA1 Expression and Cholesterol Efflux*

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Liver X Receptor β (LXRβ) Interacts Directly with ATP-binding Cassette A1 (ABCA1) to Promote High Density Lipoprotein Formation during Acute Cholesterol Accumulation*

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Liver X Receptor β (LXRβ) Interacts Directly with ATP-binding Cassette A1 (ABCA1) to Promote High Density Lipoprotein Formation during Acute Cholesterol Accumulation

Inhibition of ERK1/2 and Activation of Liver X Receptor Synergistically Induce Macrophage ABCA1 Expression and Cholesterol Efflux

Direct Interaction of Nuclear Liver X Receptor-β with ABCA1 Modulates Cholesterol Efflux* S⃞

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