Evidence map›Paper›PMID 24025715›Full record

ArticleMolecular biology of the cell2013

Sterol-induced dislocation of 3-hydroxy-3-methylglutaryl coenzyme A reductase from membranes of permeabilized cells.

Rania Elsabrouty, Youngah Jo, Tammy T Dinh, Russell A DeBose-Boyd

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Allosteric regulation of UBIAD1 trafficking from ER to Golgi revealed by chemical genetic screening.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Direct binding to sterols accelerates endoplasmic reticulum-associated degradation of HMG CoA reductase.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Review
  5. Post-Translational Regulation of HMG CoA Reductase.Cold Spring Harbor perspectives in biology · 2022
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Rania ElsabroutyHoward Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046.
Youngah Jo
Tammy T Dinh
Russell A DeBose-Boyd
Howard Hughes Medical Institute · US

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI RUSSELL, DAVID W. · 1985 to 2021
$103.1M
Dissecting ER-Associated Degradation of a Membrane Protein in Drosophila S2 CellsR01GM090216 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI DEBOSE-BOYD, RUSSELL ALFRED · 2010 to 2013
$1.3M
Howard Hughes Medical InstituteNHLBI NIH HHS HL20948NHLBI NIH HHS P01 HL020948NIGMS NIH HHS GM090216NIGMS NIH HHS R01 GM090216
6 · The paper itself

Abstract

The polytopic endoplasmic reticulum (ER)-localized enzyme 3-hydroxy-3-methylglutaryl CoA reductase catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids. Excess sterols cause the reductase to bind to ER membrane proteins called Insig-1 and Insig-2, which are carriers for the ubiquitin ligases gp78 and Trc8. The resulting gp78/Trc8-mediated ubiquitination of reductase marks it for recognition by VCP/p97, an ATPase that mediates subsequent dislocation of reductase from ER membranes into the cytosol for proteasomal degradation. Here we report that in vitro additions of the oxysterol 25-hydroxycholesterol (25-HC), exogenous cytosol, and ATP trigger dislocation of ubiquitinated and full-length forms of reductase from membranes of permeabilized cells. In addition, the sterol-regulated reaction requires the action of Insigs, is stimulated by reagents that replace 25-HC in accelerating reductase degradation in intact cells, and is augmented by the nonsterol isoprenoid geranylgeraniol. Finally, pharmacologic inhibition of deubiquitinating enzymes markedly enhances sterol-dependent ubiquitination of reductase in membranes of permeabilized cells, leading to enhanced dislocation of the enzyme. Considered together, these results establish permeabilized cells as a viable system in which to elucidate mechanisms for postubiquitination steps in sterol-accelerated degradation of reductase.

Indexed as

Adenosine TriphosphatasesAnimalsCell Cycle ProteinsCell LineCell Membrane PermeabilityCHO CellsCricetinaeCricetulusCytosolEndoplasmic ReticulumFibroblastsHumansHydroxycholesterolsHydroxymethylglutaryl CoA ReductasesImmunoblottingIntracellular Membranes25-hydroxycholesterolAdenosine TriphosphatasesCell Cycle ProteinsHydroxycholesterolsHydroxymethylglutaryl CoA ReductasesINSIG1 protein, humanINSIG2 protein, humanIntracellular Signaling Peptides and ProteinsMembrane ProteinsSterolsValosin Containing ProteinVCP protein, humanVcp protein, rat

Identifiers

PMID24025715
PMCPMC3814148
OpenAlexW1970821049

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.