Sterol-dependent nuclear import of ORP1S promotes LXR regulated trans-activation of apoE

Journal Article · Mon Oct 01 04:00:00 EDT 2012 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2012.06.012· OSTI ID:22212608

Lee, Sungsoo ^[1]; Wang, Ping-Yuan ^[1]; Jeong, Yangsik; Mangelsdorf, David J. ^[2]; Anderson, Richard G.W. ^[1]; Michaely, Peter ^[1]

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1. Departments of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039 (United States)
2. Departments of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041 (United States)

Oxysterol binding protein related protein 1S (ORP1S) is a member of a family of sterol transport proteins. Here we present evidence that ORP1S translocates from the cytoplasm to the nucleus in response to sterol binding. The sterols that best promote nuclear import of ORP1S also activate the liver X receptor (LXR) transcription factors and we show that ORP1S binds to LXRs, promotes binding of LXRs to LXR response elements (LXREs) and specifically enhances LXR-dependent transcription via the ME.1 and ME.2 enhancer elements of the apoE gene. We propose that ORP1S is a cytoplasmic sterol sensor, which transports sterols to the nucleus and promotes LXR-dependent gene transcription through select enhancer elements. -- Highlights: Black-Right-Pointing-Pointer ORP1S translocates to the nucleus in response to sterol binding. Black-Right-Pointing-Pointer The sterols that best promote nuclear import of ORP1S are LXR agonists. Black-Right-Pointing-Pointer ORP1S binds to LXRs, enhances binding of LXRs to LXREs and promotes LXR-dependent transcription of apoE.

• OSTI ID: 22212608
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 16 Vol. 318; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL NUCLEI
CYTOPLASM
GENES
LIVER
RECEPTORS
STEROLS
TRANSCRIPTION
TRANSCRIPTION FACTORS