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

Sungsoo Lee, Ping Yuan Wang, Yangsik Jeong, David J. Mangelsdorf, Richard G W Anderson, Peter Michaely

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2128-2142
Number of pages15
JournalExperimental Cell Research
Volume318
Issue number16
DOIs
StatePublished - Oct 1 2012

Keywords

  • LXR
  • NLS
  • Nuclear import
  • ORP1
  • ORP1S
  • Oxysterol

ASJC Scopus subject areas

  • Cell Biology

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