CoChat
Sign Up
Cited by 104

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR

Wang, Yan, Huang, Yongcheng, Hobbs, Helen H., Cohen, Jonathan C.·2012·Journal of Lipid Research
DOI 10.1194/jlr.m028563PMC PMC3413232
Open this paper in CoChat — free account

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 · 10.1194/jlr.m028563

Cites

8 of 8 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?

  • At the cell surface, the catalytic domain of PCSK9 binds to the EGF-A repeat of the LDLR extracellular domain and the LDLR:PCSK9 complex is internalized through clathrin-coated pits.

    “At the cell surface, the catalytic domain of PCSK9 binds to the EGF-A repeat of the LDLR extracellular domain and the LDLR:PCSK9 complex is internalized through clathrin-coated pits119,120.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [120]

    The paper’s introductory passage says PCSK9 binds the LDLR’s EGF-A repeat at the cell surface, and the Results section reports that the PCSK9–LDLR complex uses clathrin-mediated endocytosis. Our copy does not specify that PCSK9’s catalytic domain is the part that binds EGF-A. No page numbers are provided for these passages. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The PCSK9 route does not require ESCRT-mediated sorting and is a clathrin-dependent process that capitalizes on the same cellular machinery used for LDL endocytosis.

    “In contrast to IDOL-stimulated degradation of the LDLR, the PCSK9 route does not require ESCRT-mediated sorting and is a clathrin-dependent process that capitalizes on the same cellular machinery used for LDL endocytosis ( 55 ).”

    From The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation (2013) · cites this paper as [55]

    The Results section ('PCSK9-mediated LDLR degradation requires clathrin-mediated endocytosis') says the PCSK9–LDLR complex uses the same endocytic machinery that imports LDL. The ESCRT Results section says degradation does not require the first ESCRT components tested, but explicitly allows that the complex may enter the pathway downstream. The claim overstates that qualified finding as independence from ESCRT-mediated sorting altogether. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Plasma LDL particle concentration is regulated by the balance between synthesis and uptake from the circulation via the LDL receptor (LDLR).

    “Plasma LDL particle concentration is regulated by the balance between synthesis and uptake from the circulation via the LDL receptor (LDLR)2.”

    From RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels (2023) · cites this paper as [2]

  • PCSK9-mediated degradation of LDLR likely does not involve commonly used pathways for lysosomal or proteasomal degradation, since PCSK9 still promotes LDLR degradation when ubiquitination, ESCRT machinery, autophagocytic pathways, or proteasomal activity are inhibited.

    “It is also likely that PCSK9-mediated degradation of LDLR does not involve commonly used pathways for lysosomal or proteasomal degradation since PCSK9 is still able to promote LDLR degradation when ubiquitination, ESCRT machinery, autophagocytic pathways, or proteasomal activity are inhibited120.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [120]

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: 53

  1. Goldstein, 2009, The LDL receptor, Arterioscler. Thromb. Vasc. Biol., 29, 431, 10.1161/ATVBAHA.108.179564 · DOI · Paper page
  2. Maxwell, 2004, Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype, Proc. Natl. Acad. Sci. USA., 101, 7100, 10.1073/pnas.0402133101 · DOI · Paper page
  3. Abifadel, 2003, Mutations in PCSK9 cause autosomal dominant hypercholesterolemia, Nat. Genet., 34, 154, 10.1038/ng1161 · DOI · Paper page
  4. Timms, 2004, A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree, Hum. Genet., 114, 349, 10.1007/s00439-003-1071-9 · DOI
  5. Seidah, 2003, The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation, Proc. Natl. Acad. Sci. USA., 100, 928, 10.1073/pnas.0335507100 · DOI · Paper page
  6. Lagace, 2006, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice, J. Clin. Invest., 116, 2995, 10.1172/JCI29383 · DOI · Paper page
  7. Horton, 2009, PCSK9: a convertase that coordinates LDL catabolism, J. Lipid Res., 50, S172, 10.1194/jlr.R800091-JLR200 · DOI · Paper page
  8. Rudenko, 2002, Structure of the LDL receptor extracellular domain at endosomal pH, Science., 298, 2353, 10.1126/science.1078124 · DOI · Paper page
  9. Zhang, 2007, Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation, J. Biol. Chem., 282, 18602, 10.1074/jbc.M702027200 · DOI · Paper page
  10. Zhang, 2008, Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor, Proc. Natl. Acad. Sci. USA., 105, 13045, 10.1073/pnas.0806312105 · DOI · Paper page
  11. Fisher, 2007, Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation, J. Biol. Chem., 282, 20502, 10.1074/jbc.M701634200 · DOI · Paper page
  12. Cunningham, 2007, Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia, Nat. Struct. Mol. Biol., 14, 413, 10.1038/nsmb1235 · DOI · Paper page
  13. Holla, 2011, Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors, J. Lipid Res., 52, 1787, 10.1194/jlr.M018093 · DOI · Paper page
  14. Tveten, 2012, Interaction between the ligand-binding domain of the LDL receptor and the C-terminal domain of PCSK9 is required for PCSK9 to remain bound to the LDL receptor during endosomal acidification, Hum. Mol. Genet., 21, 1402, 10.1093/hmg/ddr578 · DOI · Paper page
  15. Yamamoto, 2011, A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor, J. Biol. Chem., 286, 5464, 10.1074/jbc.M110.199042 · DOI · Paper page
  16. van Driel, 1987, First cysteine-rich repeat in ligand-binding domain of low density lipoprotein receptor binds Ca2+ and monoclonal antiobodies, but not lipoproteins, J. Biol. Chem., 262, 17443, 10.1016/S0021-9258(18)45399-9 · DOI
  17. Russell, 1984, Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor, Cell., 37, 577, 10.1016/0092-8674(84)90388-X · DOI · Paper page
  18. Wilund, 2002, Molecular mechanisms of autosomal recessive hypercholesterolemia, Hum. Mol. Genet., 11, 3019, 10.1093/hmg/11.24.3019 · DOI · Paper page
  19. Liscum, 1983, Regulation of 3-hydroxy-3-methylglutaryl Coenzyme A reductase and its mRNA in rat liver as studied with a monoclonal antibody and a cDNA probe, J. Biol. Chem., 258, 8450, 10.1016/S0021-9258(20)82085-7 · DOI
  20. Shimomura, 1997, Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells, J. Clin. Invest., 99, 838, 10.1172/JCI119247 · DOI
  21. Qu, 2007, Autophagy gene-dependent clearance of apoptotic cells during embryonic development, Cell., 128, 931, 10.1016/j.cell.2006.12.044 · DOI
  22. Garcia, 2001, Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein, Science., 292, 1394, 10.1126/science.1060458 · DOI · Paper page
  23. Horton, 2007, Molecular biology of PCSK9: its role in LDL metabolism, Trends Biochem. Sci., 32, 71, 10.1016/j.tibs.2006.12.008 · DOI · Paper page
  24. Brown, 1976, Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein, Cell., 9, 663, 10.1016/0092-8674(76)90130-6 · DOI
  25. Goldstein, 1977, Genetics of the LDL receptor: evidence that the mutations affecting binding and internalization are allelic, Cell., 12, 629, 10.1016/0092-8674(77)90263-X · DOI
  26. Garcia, 2001, Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein, Science., 292, 1394, 10.1126/science.1060458 · DOI · Paper page
  27. Pearse, 1990, Clathrin, adaptors, and sorting, Annu. Rev. Cell Biol., 6, 151, 10.1146/annurev.cb.06.110190.001055 · DOI
  28. Sigismund, 2005, Clathrin-independent endocytosis of ubiquitinated cargos, Proc. Natl. Acad. Sci. USA., 102, 2760, 10.1073/pnas.0409817102 · DOI · Paper page
  29. Mayor, 2007, Pathways of clathrin-independent endocytosis, Nat. Rev. Mol. Cell Biol., 8, 603, 10.1038/nrm2216 · DOI · Paper page
  30. Zelcer, 2009, LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor, Science., 325, 100, 10.1126/science.1168974 · DOI · Paper page
  31. Jo, 2011, Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8, Proc. Natl. Acad. Sci. USA., 108, 20503, 10.1073/pnas.1112831108 · DOI
  32. Maxwell, 2005, Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment, Proc. Natl. Acad. Sci. USA., 102, 2069, 10.1073/pnas.0409736102 · DOI · Paper page
  33. Cancino, 2007, Antibody to AP1B adaptor blocks biosynthetic and recycling routes of basolateral proteins at recycling endosomes, Mol. Biol. Cell., 18, 4872, 10.1091/mbc.e07-06-0563 · DOI · Paper page
  34. Barth, 2010, Autophagy: assays and artifacts, J. Pathol., 221, 117, 10.1002/path.2694 · DOI
  35. Raiborg, 2009, The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins, Nature., 458, 445, 10.1038/nature07961 · DOI · Paper page
  36. Raiborg, 2008, Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking, Exp. Cell Res., 314, 801, 10.1016/j.yexcr.2007.10.014 · DOI
  37. Razi, 2006, Distinct roles for Tsg101 and Hrs in multivesicular body formation and inward vesiculation, Mol. Biol. Cell., 17, 3469, 10.1091/mbc.e05-11-1054 · DOI
  38. Komada, 1999, Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis, Genes Dev., 13, 1475, 10.1101/gad.13.11.1475 · DOI · Paper page
  39. Gullapalli, 2006, An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins, Mol. Biol. Cell., 17, 1228, 10.1091/mbc.e05-09-0899 · DOI
  40. Dores, 2012, ALIX binds a YPX3L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting, J. Cell Biol., 197, 407, 10.1083/jcb.201110031 · DOI
  41. Haugsten, 2011, Clathrin- and dynamin-independent endocytosis of FGFR3–implications for signalling, PLoS ONE., 6, e21708, 10.1371/journal.pone.0021708 · DOI
  42. Eden, 2002, Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1, J. Clin. Invest., 110, 1695, 10.1172/JCI0216445 · DOI · Paper page
  43. Norman, 1999, Characterization of a novel cellular defect in patients with phenotypic homozygous familial hypercholesterolemia, J. Clin. Invest., 104, 619, 10.1172/JCI6677 · DOI · Paper page
  44. Meyer, 2011, PEST motif serine and tyrosine phosphorylation controls vascular endothelial growth factor receptor 2 stability and downregulation, Mol. Cell. Biol., 31, 2010, 10.1128/MCB.01006-10 · DOI
  45. Hewitt, 2002, Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation, EMBO J., 21, 2418, 10.1093/emboj/21.10.2418 · DOI
  46. Mizuno, 2011, Ubiquitination is associated with lysosomal degradation of cell surface-resident ATP-binding cassette transporter A1 (ABCA1) through the endosomal sorting complex required for transport (ESCRT) pathway, Hepatology., 54, 631, 10.1002/hep.24387 · DOI
  47. Williams, 2007, The emerging shape of the ESCRT machinery, Nat. Rev. Mol. Cell Biol., 8, 355, 10.1038/nrm2162 · DOI
  48. Berlin, 2010, Regulation of epidermal growth factor receptor ubiquitination and trafficking by the USP8.STAM complex, J. Biol. Chem., 285, 34909, 10.1074/jbc.M109.016287 · DOI · Paper page
  49. Knoblauch, 2000, A cholesterol-lowering gene maps to chromosome 13q, Am. J. Hum. Genet., 66, 157, 10.1086/302704 · DOI
  50. Park, 2004, Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver, J. Biol. Chem., 279, 50630, 10.1074/jbc.M410077200 · DOI · Paper page
  51. Benjannet, 2004, NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the LDLR and LDL-cholesterol, J. Biol. Chem., 279, 48865, 10.1074/jbc.M409699200 · DOI · Paper page
  52. Sigismund, 2008, Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation, Dev. Cell., 15, 209, 10.1016/j.devcel.2008.06.012 · DOI
  53. Bache, 2003, STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes, J. Biol. Chem., 278, 12513, 10.1074/jbc.M210843200 · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Wang, Y., Huang, Y., Hobbs, H. H., & Cohen, J. C.
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2012-09
Volume
53
Issue
9
Pages
1932-1943
ISSN
0022-2275
DOI
10.1194/jlr.m028563
PMC
PMC3413232
Cited by
104
References
8
Language
en
Licence

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