CoChat
Sign Up
Cited by 556

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig

Radhakrishnan, Arun, Ikeda, Yukio, Kwon, Hyock Joo, Brown, Michael S., Goldstein, Joseph L.·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0700899104
Open this paper in CoChat — free account

Abstract

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.0700899104

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • When preincubated with 25-hydroxycholesterol, LDLR reduction is similar in WT and NPC1−/− cells.

    “When the cells were preincubated with 25-hydroxycholesterol, which inhibits SREBP processing without traversing the lysosome (16), the LDLR reduction was similar in WT and NPC1−/− cells (Fig. 1 B, Right).”

    From Last step in the path of LDL cholesterol from lysosome to plasma membrane to ER is governed by phosphatidylserine (2020) · cites this paper as [16]

    The Results report that 25-hydroxycholesterol inhibits SREBP-2 cleavage, supporting that part of the explanation attached to this citation. Our copy does not establish that it acts without traversing the lysosome. The WT-versus-NPC1−/− LDLR comparison is attributed to the citing paper’s own Fig. 1, not to this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • INSIG1 is ubiquitinated and degraded by GP78 when oxysterols are depleted, while oxysterols stabilize it by binding within its transmembrane domains.

    “INSIG1 is ubiquitinated and degraded by GP78 when oxysterols are depleted, while oxysterols stabilize it by binding within its transmembrane domains (37, 38).”

    From Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression (2021) · cites this paper as [38]

    The Abstract reports that oxysterols bind Insigs and that the third and fourth transmembrane helices are important for binding. The Discussion says the binding experiments used Insig-2, though the authors believe the conclusions also apply to Insig-1. Our copy does not say that oxysterol binding stabilizes Insig-1 or that GP78 ubiquitinates and degrades it upon oxysterol depletion; its Discussion instead describes ubiquitination and degradation of HMGR. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

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

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 39

  1. 10.1016/S0092-8674(00)80213-5 · DOI · Paper page
  2. 10.1016/S1388-1981(00)00140-2 · DOI
  3. 10.1016/j.cell.2005.12.022 · DOI · Paper page
  4. 10.1016/S0092-8674(00)80675-3 · DOI · Paper page
  5. 10.1101/gad.891301 · DOI · Paper page
  6. 10.1016/S0021-9258(19)43148-7 · DOI
  7. 10.1016/S0021-9258(19)42106-6 · DOI · Paper page
  8. JL Goldstein, JR Faust, GY Brunschede, MS Brown Lipids, Lipoproteins, and Drugs, eds D Kritchevsky, R Paoletti, WL Holmes (Plenum, New York), pp. 77–84 (1975). · DOI
  9. 10.1126/science.663671 · DOI
  10. 10.1016/S0021-9258(19)43901-X · DOI
  11. 10.1172/JCI0216388 · DOI
  12. 10.1016/S1388-1981(00)00142-6 · DOI · Paper page
  13. 10.1016/S0076-6879(03)64002-4 · DOI
  14. 10.1074/jbc.M504041200 · DOI · Paper page
  15. 10.1146/annurev.cellbio.20.010403.105307 · DOI · Paper page
  16. 10.1074/jbc.273.43.28261 · DOI
  17. 10.1016/S0092-8674(00)00037-4 · DOI
  18. 10.1016/S0092-8674(02)00872-3 · DOI · Paper page
  19. 10.1074/jbc.M410302200 · DOI
  20. 10.1016/j.molcel.2004.06.019 · DOI · Paper page
  21. 10.1016/S1097-2765(02)00591-9 · DOI · Paper page
  22. 10.1073/pnas.0700907104 · DOI
  23. 10.1063/1.1733852 · DOI
  24. 10.1021/bi00713a027 · DOI
  25. 10.1074/jbc.M312623200 · DOI
  26. 10.1016/j.cmet.2005.01.001 · DOI
  27. 10.1021/jm00002a010 · DOI
  28. 10.1074/jbc.M108348200 · DOI
  29. 10.1073/pnas.162488899 · DOI · Paper page
  30. 10.1074/jbc.M306476200 · DOI
  31. 10.1073/pnas.0601923103 · DOI
  32. 10.1016/j.cmet.2005.11.014 · DOI · Paper page
  33. 10.1016/S0022-2275(20)32042-3 · DOI
  34. 10.1194/jlr.M200293-JLR200 · DOI
  35. 10.1038/nature03923 · DOI
  36. 10.1016/S1097-2765(02)00822-5 · DOI
  37. 10.1074/jbc.274.40.28549 · DOI · Paper page
  38. 10.1074/jbc.272.32.20213 · DOI · Paper page
  39. 10.1074/jbc.270.20.12152 · DOI

Cited by

Sorted by citations

Metadata

Authors
Radhakrishnan, A., Ikeda, Y., Kwon, H. J., Brown, M. S., & Goldstein, J. L.
Affiliations
  • Departments of *Molecular Genetics and
  • Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-04-17
Volume
104
Issue
16
Pages
6511-6518
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0700899104
Cited by
556
References
2
Language
en

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