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Brief Review

Feedback Regulation of Cholesterol Uptake by the LXR–IDOL–LDLR Axis

Li Zhang, Karen Reue, Loren G. Fong, Stephen G. Young, Peter Tontonoz
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https://doi.org/10.1161/ATVBAHA.112.250571
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:2541-2546
Originally published October 17, 2012
Li Zhang
From the Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute (L.Z., P.T.), and Department of Human Genetics and Medicine, David Geffen School of Medicine (K.R., L.G.F., S.G.), University of California Los Angeles, Los Angeles, CA.
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Karen Reue
From the Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute (L.Z., P.T.), and Department of Human Genetics and Medicine, David Geffen School of Medicine (K.R., L.G.F., S.G.), University of California Los Angeles, Los Angeles, CA.
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Loren G. Fong
From the Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute (L.Z., P.T.), and Department of Human Genetics and Medicine, David Geffen School of Medicine (K.R., L.G.F., S.G.), University of California Los Angeles, Los Angeles, CA.
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Stephen G. Young
From the Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute (L.Z., P.T.), and Department of Human Genetics and Medicine, David Geffen School of Medicine (K.R., L.G.F., S.G.), University of California Los Angeles, Los Angeles, CA.
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Peter Tontonoz
From the Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute (L.Z., P.T.), and Department of Human Genetics and Medicine, David Geffen School of Medicine (K.R., L.G.F., S.G.), University of California Los Angeles, Los Angeles, CA.
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  • Article
    • Abstract
    • Introduction
    • Role of LDLR in Cholesterol Homeostasis
    • Regulation of IDOL Expression by LXR
    • IDOL Mediates Ubiquitination and Degradation of the LDLR
    • VLDLR and ApoER2 Are Also Targets for IDOL-Mediated Degradation
    • Complementary Regulation of the LDLR by the SREBP and the IDOL Pathways
    • The Structural Basis for Substrate Recognition by IDOL
    • Structural Basis of IDOL-Mediated LDLR Ubiquitination
    • Involvement of IDOL in Human Cholesterol Metabolism
    • Sources of Funding
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    • References
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Abstract

Inducible degrader of the low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the low-density lipoprotein receptor (LDLR). IDOL expression is controlled at the transcriptional level by the cholesterol-sensing nuclear receptor liver X receptor (LXR). In response to rising cellular sterol levels, activated LXR induces IDOL production, thereby limiting further uptake of exogenous cholesterol through the LDLR pathway. The LXR–IDOL–LDLR mechanism for feedback inhibition of cholesterol uptake is independent of and complementary to the sterol regulatory element–binding protein pathway. Since the initial description of the LXR–IDOL pathway, biochemical studies have helped to define the structural basis for both IDOL target recognition and LDLR ubiquitin transfer. Recent work has also suggested links between IDOL and human lipid metabolism.

  • atherosclerosis
  • cholesterol-lowering drugs
  • lipoproteins
  • metabolism
  • molecular biology
  • Received July 10, 2012.
  • Accepted August 17, 2012.
  • © 2012 American Heart Association, Inc.
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Arteriosclerosis, Thrombosis, and Vascular Biology
November 2012, Volume 32, Issue 11
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Jump to

  • Article
    • Abstract
    • Introduction
    • Role of LDLR in Cholesterol Homeostasis
    • Regulation of IDOL Expression by LXR
    • IDOL Mediates Ubiquitination and Degradation of the LDLR
    • VLDLR and ApoER2 Are Also Targets for IDOL-Mediated Degradation
    • Complementary Regulation of the LDLR by the SREBP and the IDOL Pathways
    • The Structural Basis for Substrate Recognition by IDOL
    • Structural Basis of IDOL-Mediated LDLR Ubiquitination
    • Involvement of IDOL in Human Cholesterol Metabolism
    • Sources of Funding
    • Disclosures
    • References
  • Figures & Tables
  • Info & Metrics
  • eLetters

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    Feedback Regulation of Cholesterol Uptake by the LXR–IDOL–LDLR Axis
    Li Zhang, Karen Reue, Loren G. Fong, Stephen G. Young and Peter Tontonoz
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:2541-2546, originally published October 17, 2012
    https://doi.org/10.1161/ATVBAHA.112.250571

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    Feedback Regulation of Cholesterol Uptake by the LXR–IDOL–LDLR Axis
    Li Zhang, Karen Reue, Loren G. Fong, Stephen G. Young and Peter Tontonoz
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:2541-2546, originally published October 17, 2012
    https://doi.org/10.1161/ATVBAHA.112.250571
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