Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein

Xianxin Hua, Axel Nohturfft, Joseph L. Goldstein, Michael S. Brown

Research output: Contribution to journalArticle

406 Scopus citations

Abstract

Through expression cloning we have isolated a cDNA-encoding SREBP cleavage-activating protein (SCAP), which regulates cholesterol metabolism by stimulating cleavage of transcription factors SREBP-1 and -2, thereby releasing them from membranes. The cDNA was isolated from Chinese hamster ovary cells with a dominant mutation that renders them resistant to sterol- mediated suppression of cholesterol synthesis and uptake. Sterol resistance was traced to a G→A transition at codon 443 of SCAP, changing aspartic acid to asparagine. The D443N mutation enhances the cleavage-stimulating ability of SCAP and renders it resistant to inhibition by sterols. SCAP has multiple membrane-spanning regions, five of which resemble the sterol-sensing domain of HMG CoA reductase, an endoplasmic reticulum enzyme whose degradation is accelerated by sterols. SCAP appears to be a central regulator of cholesterol metabolism in animal cells.

Original languageEnglish (US)
Pages (from-to)415-426
Number of pages12
JournalCell
Volume87
Issue number3
DOIs
StatePublished - Nov 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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