PMID: 8942999Nov 26, 1996Paper

Recurrent G-to-A substitution in a single codon of SREBP cleavage-activating protein causes sterol resistance in three mutant Chinese hamster ovary cell lines

Proceedings of the National Academy of Sciences of the United States of America
A NohturfftJ L Goldstein

Abstract

Oxygenated sterols such as 25-hydroxycholesterol kill Chinese hamster ovary cells because they inhibit the proteolytic processing of sterol regulatory element binding proteins (SREBPs), a pair of membrane-bound transcription factors that activate genes controlling cholesterol synthesis and uptake from lipoproteins. The unprocessed SREBPs remain membrane-bound, they cannot activate the cholesterol biosynthetic pathway, and the cells die of cholesterol deprivation. Several sterol-resistant hamster cell lines have been isolated previously by chemical mutagenesis and selection for resistance to killing by 25-hydroxycholesterol. We recently identified the defect in one such cell line (25-RA cells) as a point mutation in a newly discovered membrane protein of 1276 amino acids, designated SREBP cleavage-activating protein (SCAP). The mutation in the 25-RA cells resulted from a G-to-A transition in codon 443 of the SCAP gene, changing aspartic acid to asparagine. Wild-type SCAP, when overexpressed by transfection, stimulates the proteolytic processing of both SREBPs. The D443N substitution is an activating mutation that increases the activity of SCAP and renders it resistant to inhibition by 25-hydroxycholesterol. We here report the id...Continue Reading

References

Apr 1, 1975·Journal of Cellular Physiology·A A Kandutsch, H W Chen
Feb 1, 1990·Nature·J L Goldstein, M S Brown
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M OritaT Sekiya
Feb 24, 1988·Biochimica Et Biophysica Acta·S Leonard, M Sinensky
Apr 4, 1986·Science·M S Brown, J L Goldstein
May 1, 1995·Toxicology Letters·A A van ZeelandH Vrieling
Sep 15, 1995·The Journal of Biological Chemistry·G GuanI Shechter
Jan 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·J EricssonP A Edwards

❮ Previous
Next ❯

Citations

Nov 19, 2002·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lorraine SalekA J Marian
May 4, 2000·Progress in Lipid Research·N D RidgwayM K Storey
Jan 20, 2005·The Journal of Biological Chemistry·Yan WangAxel Nohturfft
Apr 29, 1998·Current Opinion in Lipidology·R Y Hampton
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Randolph Y Hampton
Apr 22, 2009·PloS One·Sandipan ChatterjeeRajeev Sivasankaran
Jun 30, 2000·Biochemical and Biophysical Research Communications·D ThewkeM S Sinensky
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·S ScheekJ L Goldstein
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·A NohturfftJ L Goldstein
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·M S Brown, J L Goldstein
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A NohturfftM S Brown
Feb 1, 2002·Developmental Biology·Ronald L JohnsonEvans C Bailey
Jan 27, 2005·Molecular Genetics and Metabolism·Lina S Correa-Cerro, Forbes D Porter
Nov 9, 2006·Journal of Lipid Research·Peter C W LeeRussell A Debose-Boyd
Mar 17, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Koh OnoKoji Hasegawa
Aug 19, 2003·Nature Reviews. Molecular Cell Biology·Robert B Rawson
May 21, 2010·Critical Reviews in Biochemistry and Molecular Biology·Youngah Jo, Russell A Debose-Boyd
Jun 27, 1998·The Journal of Biological Chemistry·A NohturfftJ L Goldstein
Sep 2, 2004·Molecular and Cellular Biology·Julia I TothTimothy F Osborne
Oct 1, 2004·World Journal of Gastroenterology : WJG·Lutz-W WeberAndreas Stampfl
Jan 5, 2000·Physiological Reviews·G J Schroepfer
Feb 8, 2002·Developmental Cell·Adam C SeegmillerRobert B Rawson
Oct 7, 2004·Biochimica Et Biophysica Acta·Katsumi HigakiStephen L Sturley

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.