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The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver

Park, Sahng Wook, Moon, Young-Ah, Horton, Jay D.·2004·Journal of Biological Chemistry
DOI 10.1074/jbc.m410077200
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Crossref · 10.1074/jbc.m410077200

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4 of 4 references verified0 citation errors · 0 not checkable

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  • The endosomal-lysosomal mechanism is dependent on ARH adaptor protein-mediated internalization of the PCSK9 (C-form)-LDLr complex into the endocytic pathway.

    “The endosomal-lysosomal mechanism is dependent on autosomal recessive hypercholesterolaemia (ARH) adaptor proteinmediated internalization of the PCSK9 (C-form)-LDLr complex into the endocytic pathway (Park et al, 2004;Qian et al, 2007).”

    From PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1 (2008) · cites this paper as Park et al, 2004

    The Results passage describing Fig. 6 reports that PCSK9 reduced hepatic LDLR protein even in mice lacking ARH. The Discussion likewise says the effect was not dependent on functional ARH and appeared to act before LDLR internalization, contrary to the claimed ARH-dependent mechanism. (LLM, conf=0.91)

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  • PCSK9 remains bound to LDLR within the acidic endosomal environment, preventing the acid-induced conformational changes required for receptor recycling and directing the receptor towards lysosomal degradation.

    “However, unlike LDL, PCSK9 remains bound to LDLR within the acidic endosomal environment, preventing the acid-induced conformational changes required for receptor recycling and thus directs the receptor towards lysosomal degradation.”

    From The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms (2025) · cites this paper as [13]

    The Discussion (page unavailable) says PCSK9 appears to reduce LDLR through a mechanism acting before internalization and recycling, possibly while the receptor is moving to or is on the cell surface. Although it supports PCSK9-mediated LDLR degradation, it places the effect before endosomal recycling rather than attributing it to persistent binding in acidic endosomes or blocked conformational changes. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

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  • The post-ER mechanism of PCSK9-mediated LDLr disposal requires the proteolytic activity of PCSK9.

    “The post-ER mechanism requires the proteolytic activity of PCSK9, whereas the endosomallysosomal mechanism does not (Park et al, 2004;McNutt et al, 2007).”

    From PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1 (2008) · cites this paper as Park et al, 2004

    The Results passage under Fig. 2 reports that catalytically inactive PCSK9 did not reduce liver LDLR protein, suggesting dependence on a functional catalytic domain. But the same passage places LDLR reduction either between receptor synthesis in the ER and arrival at the cell surface or at the surface; it does not establish a specifically post-ER mechanism or show that proteolytic activity is required independently of PCSK9's autocatalytic processing. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PCSK9 is a secreted protein that binds to the LDLR ectodomain and promotes its degradation.

    “One of the most well-documented mechanisms involves PCSK9 [13][14][15].PCSK9 binds to the ectodomain of LDLR at the cell surface and is internalized together with the receptor.”

    From The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms (2025) · cites this paper as [13]

    The Results and Discussion (page unavailable) report that PCSK9 overexpression reduces LDLR protein, supporting the degradation part of the claim. But the Discussion leaves open whether PCSK9 acts as a secreted protein and says its effect appears to occur before LDLR internalization; it does not establish ectodomain binding or co-internalization. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The endosomal-lysosomal mechanism of PCSK9-mediated LDLr disposal does not require the proteolytic activity of PCSK9.

    “The post-ER mechanism requires the proteolytic activity of PCSK9, whereas the endosomallysosomal mechanism does not (Park et al, 2004;McNutt et al, 2007).”

    From PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1 (2008) · cites this paper as Park et al, 2004

    The paper reports that catalytically inactive PCSK9 did not reduce LDLR protein in mouse liver (Fig. 5; Discussion). Its Discussion places the observed effect before LDLR internalization, but does not test whether an endosomal–lysosomal mechanism requires proteolytic activity. Searches for that mechanism and for endosomal or lysosomal degradation found no passage establishing the claimed exception. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

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Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 41

  1. Goldstein, 1977, Annu. Rev. Biochem., 46, 897, 10.1146/annurev.bi.46.070177.004341 · DOI · Paper page
  2. Dietschy, 1993, J. Lipid Res., 34, 1637, 10.1016/S0022-2275(20)35728-X · DOI · Paper page
  3. Brown, 1997, Cell, 89, 331, 10.1016/S0092-8674(00)80213-5 · DOI · Paper page
  4. Horton, 2003, Proc. Natl. Acad. Sci. U. S. A., 100, 12027, 10.1073/pnas.1534923100 · DOI · Paper page
  5. Seidah, 2003, Proc. Natl. Acad. Sci. U. S. A., 100, 928, 10.1073/pnas.0335507100 · DOI · Paper page
  6. Abifadel, 2003, Nat. Genet., 34, 154, 10.1038/ng1161 · DOI · Paper page
  7. Leren, 2004, Clin. Genet., 65, 419, 10.1111/j.0009-9163.2004.0238.x · DOI
  8. Timms, 2004, Hum. Genet., 114, 349, 10.1007/s00439-003-1071-9 · DOI
  9. Rader, 2003, J. Clin. Invest., 111, 1795, 10.1172/JCI200318925 · DOI · Paper page
  10. Shimano, 1996, J. Clin. Invest., 98, 1575, 10.1172/JCI118951 · DOI
  11. Horton, 1999, J. Clin. Invest., 103, 1067, 10.1172/JCI6246 · DOI
  12. Goldstein, 1983, Methods Enzymol., 98, 241, 10.1016/0076-6879(83)98152-1 · DOI
  13. Hua, 1996, J. Biol. Chem., 271, 10379, 10.1074/jbc.271.17.10379 · DOI
  14. Espenshade, 1999, J. Biol. Chem., 274, 22795, 10.1074/jbc.274.32.22795 · DOI · Paper page
  15. Russell, 1984, Cell, 37, 577, 10.1016/0092-8674(84)90388-X · DOI · Paper page
  16. Herz, 1988, EMBO J., 7, 4119, 10.1002/j.1460-2075.1988.tb03306.x · DOI
  17. Herz, 1991, J. Biol. Chem., 266, 21232, 10.1016/S0021-9258(18)54845-6 · DOI · Paper page
  18. Jones, 2003, J. Biol. Chem., 278, 29024, 10.1074/jbc.M304855200 · DOI · Paper page
  19. Wang, 1994, Cell, 77, 53, 10.1016/0092-8674(94)90234-8 · DOI
  20. Shimano, 1997, J. Clin. Invest., 100, 2115, 10.1172/JCI119746 · DOI · Paper page
  21. Moon, 2003, J. Biol. Chem., 278, 7335, 10.1074/jbc.M211684200 · DOI
  22. Rawson, 1998, J. Biol. Chem., 273, 28261, 10.1074/jbc.273.43.28261 · DOI
  23. Rawson, 1999, J. Biol. Chem., 274, 28549, 10.1074/jbc.274.40.28549 · DOI · Paper page
  24. DeBose-Boyd, 1999, Cell, 99, 703, 10.1016/S0092-8674(00)81668-2 · DOI · Paper page
  25. Green, 1979, Methods Enzymol., 58, 425, 10.1016/S0076-6879(79)58157-9 · DOI
  26. Nyberg-Hoffman, 1999, Nat. Med., 5, 955, 10.1038/11400 · DOI
  27. Engelking, 2004, J. Clin. Invest., 113, 1168, 10.1172/JCI20978 · DOI · Paper page
  28. Liang, 2002, J. Biol. Chem., 277, 9520, 10.1074/jbc.M111421200 · DOI · Paper page
  29. Ishibashi, 1993, J. Clin. Invest., 92, 883, 10.1172/JCI116663 · DOI · Paper page
  30. Shimomura, 1998, Genes Dev., 12, 3182, 10.1101/gad.12.20.3182 · DOI · Paper page
  31. Yang, 2001, Proc. Natl. Acad. Sci. U. S. A., 98, 13607, 10.1073/pnas.201524598 · DOI · Paper page
  32. Goldstein, 2002, Arch. Biochem. Biophys., 397, 139, 10.1006/abbi.2001.2615 · DOI · Paper page
  33. Goldstein, 1985, Annu. Rev. Cell Biol., 1, 1, 10.1146/annurev.cb.01.110185.000245 · DOI · Paper page
  34. Garcia, 2001, Science, 292, 1394, 10.1126/science.1060458 · DOI · Paper page
  35. Norman, 1999, J. Clin. Invest., 104, 619, 10.1172/JCI6677 · DOI · Paper page
  36. Wilund, 2002, Hum. Mol. Genet., 11, 3019, 10.1093/hmg/11.24.3019 · DOI · Paper page
  37. Herz, 2001, Neuron, 29, 571, 10.1016/S0896-6273(01)00234-3 · DOI
  38. Ouguerrram, 2004, Arterioscler. Thromb. Vasc. Biol., 8, 1448, 10.1161/01.ATV.0000133684.77013.88 · DOI
  39. Maxwell, 2004, Proc. Natl. Acad. Sci. U. S. A., 101, 7100, 10.1073/pnas.0402133101 · DOI · Paper page
  40. Brown, 1975, Cell, 6, 307, 10.1016/0092-8674(75)90182-8 · DOI
  41. , Applied Biosystems (2001) User Bulletin 2, Foster City, CA

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Metadata

Authors
Park, S. W., Moon, Y.-A., & Horton, J. D.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-11
Volume
279
Issue
48
Pages
50630-50638
ISSN
0021-9258
DOI
10.1074/jbc.m410077200
Cited by
452
References
4
Language
en
Licence

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