TY - JOUR
T1 - Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein
AU - Hua, Xianxin
AU - Nohturfft, Axel
AU - Goldstein, Joseph L.
AU - Brown, Michael S.
N1 - Funding Information:
We thank Dr. T. Y. Chang for providing 25-RA cells, our colleagues David Russell and Rob Rawson for helpful discussions, Mark Daris for excellent technical assistance, Lisa Beatty for invaluable help with tissue culture, and Jeff Cormier and Michelle Laremore for synthesis of oligonucleotides and DNA sequencing. This research was supported by grants from the National Institutes of Health (HL 20948) and Perot Family Foundation.
PY - 1996/11/1
Y1 - 1996/11/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(00)81362-8
DO - 10.1016/S0092-8674(00)81362-8
M3 - Article
C2 - 8898195
AN - SCOPUS:0030298339
SN - 0092-8674
VL - 87
SP - 415
EP - 426
JO - Cell
JF - Cell
IS - 3
ER -