Cited by 987Cholesterol and Lipid MetabolismCancer, Lipids, and MetabolismLipid metabolism and biosynthesis

Crucial Step in Cholesterol Homeostasis

Open access
Yang, Tong, Espenshade, Peter J., Wright, Michael E., Yabe, Daisuke, Gong, Yi, Aebersold, Ruedi, Goldstein, Joseph L., Brown, Michael S.·2002·Cell

Abstract

Using coimmunoprecipitation and tandem mass spectrometry, we identify INSIG-1 as an ER protein that binds the sterol-sensing domain of SREBP cleavage-activating protein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER. In sterol-depleted cells, SCAP escorts SREBPs from ER to Golgi for proteolytic processing, thereby allowing SREBPs to stimulate cholesterol synthesis. Sterols induce binding of SCAP to INSIG-1, as determined by blue native-PAGE, and this is correlated with the inhibition of SCAP exit from the ER. Overexpression of INSIG-1 increases the sensitivity of cells to sterol-mediated inhibition of SREBP processing. Mutant SCAP(Y298C) fails to bind INSIG-1 and is resistant to sterol-mediated inhibition of ER exit. By facilitating sterol-dependent ER retention of SCAP, INSIG-1 plays a central role in cholesterol homeostasis.

Integrity signals

Registry

Crossref · 10.1016/s0092-8674(02)00872-3

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Yang, T., Espenshade, P. J., Wright, M. E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J. L., & Brown, M. S.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Institute for Systems Biology (US)
Corresponding author
Goldstein, Joseph L.
Venue
Cell
Publisher
Elsevier BV
Published
2002-08
Volume
110
Issue
4
Pages
489-500
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2097632838
Cited by
987
References
27
Citations by year
2026: 26 · 2025: 27 · 2024: 43 · 2023: 39 · 2022: 48 · 2021: 46 · 2020: 36 · 2019: 37 · 2018: 37 · 2017: 41 · 2016: 40 · 2015: 38 · 2014: 49 · 2013: 31 · 2012: 49
FWCI
44.77
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r33ca084698-04)
  • National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
  • National Cancer Institute (1R33 CA84698)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
INSIG1, SCAP, SREBP, cholesterol homeostasis, sterol sensing, endoplasmic reticulum retention, cholesterol biosynthesis, ER-Golgi transport, protein-protein interaction, sterol depletion
MeSH terms
Cell Membrane, Cells, Cultured, Cholesterol, DNA-Binding Proteins, Endoplasmic Reticulum, Eukaryotic Cells, Gene Expression Regulation, Genetic Vectors, Golgi Apparatus, Homeostasis, Humans, Membrane Proteins, Mutation, Peptide Hydrolases, Protein Binding, Proteins, Sterols, Transcription Factors, Transfection, Protein Structure, Tertiary, Protein Transport, CCAAT-Enhancer-Binding Proteins, Intracellular Signaling Peptides and Proteins, Sterol Regulatory Element Binding Protein 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review