Pro-protein convertase subtilisin/kexin type 9 (PCSK9)

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  1. 1.0 1.1 Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):928-33. Epub 2003 Jan 27. PMID:12552133 doi:
  2. 2.0 2.1 2.2 Abifadel M, Rabes JP, Devillers M, Munnich A, Erlich D, Junien C, Varret M, Boileau C. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat. 2009 Apr;30(4):520-9. doi: 10.1002/humu.20882. PMID:19191301 doi:
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Hess CN, Low Wang CC, Hiatt WR. PCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes. Annu Rev Med. 2017 Nov 2. doi: 10.1146/annurev-med-042716-091351. PMID:29095667 doi:
  4. Piper DE, Jackson S, Liu Q, Romanow WG, Shetterly S, Thibault ST, Shan B, Walker NP. The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol. Structure. 2007 May;15(5):545-52. PMID:17502100 doi:
  5. Naureckiene S, Ma L, Sreekumar K, Purandare U, Lo CF, Huang Y, Chiang LW, Grenier JM, Ozenberger BA, Jacobsen JS, Kennedy JD, DiStefano PS, Wood A, Bingham B. Functional characterization of Narc 1, a novel proteinase related to proteinase K. Arch Biochem Biophys. 2003 Dec 1;420(1):55-67. PMID:14622975
  6. Benjannet S, Rhainds D, Hamelin J, Nassoury N, Seidah NG. The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem. 2006 Oct 13;281(41):30561-72. Epub 2006 Aug 15. PMID:16912035 doi:
  7. Dewpura T, Raymond A, Hamelin J, Seidah NG, Mbikay M, Chretien M, Mayne J. PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans. FEBS J. 2008 Jul;275(13):3480-93. doi: 10.1111/j.1742-4658.2008.06495.x. Epub, 2008 May 22. PMID:18498363 doi:
  8. 8.0 8.1 Costet P, Cariou B, Lambert G, Lalanne F, Lardeux B, Jarnoux AL, Grefhorst A, Staels B, Krempf M. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. J Biol Chem. 2006 Mar 10;281(10):6211-8. doi: 10.1074/jbc.M508582200. Epub 2006, Jan 6. PMID:16407292 doi:
  9. Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah NG, Bernier L, Prat A. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1454-9. doi:, 10.1161/01.ATV.0000134621.14315.43. Epub 2004 Jun 3. PMID:15178557 doi:
  10. Burke AC, Dron JS, Hegele RA, Huff MW. PCSK9: Regulation and Target for Drug Development for Dyslipidemia. Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:223-244. doi:, 10.1146/annurev-pharmtox-010716-104944. Epub 2016 Aug 8. PMID:27575716 doi:
  11. Poirier S, Mayer G, Poupon V, McPherson PS, Desjardins R, Ly K, Asselin MC, Day R, Duclos FJ, Witmer M, Parker R, Prat A, Seidah NG. Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route. J Biol Chem. 2009 Oct 16;284(42):28856-64. doi: 10.1074/jbc.M109.037085. Epub, 2009 Jul 27. PMID:19635789 doi:
  12. Chen Y, Wang H, Yu L, Yu X, Qian YW, Cao G, Wang J. Role of ubiquitination in PCSK9-mediated low-density lipoprotein receptor degradation. Biochem Biophys Res Commun. 2011 Nov 25;415(3):515-8. doi:, 10.1016/j.bbrc.2011.10.110. Epub 2011 Nov 2. PMID:22074827 doi:10.1016/j.bbrc.2011.10.110
  13. Sharotri V, Collier DM, Olson DR, Zhou R, Snyder PM. Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9). J Biol Chem. 2012 Jun 1;287(23):19266-74. doi: 10.1074/jbc.M112.363382. Epub 2012, Apr 9. PMID:22493497 doi:10.1074/jbc.M112.363382
  14. Yamamoto T, Lu C, Ryan RO. A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor. J Biol Chem. 2011 Feb 18;286(7):5464-70. doi: 10.1074/jbc.M110.199042. Epub 2010 , Dec 11. PMID:21149300 doi:
  15. 15.0 15.1 Lo Surdo P, Bottomley MJ, Calzetta A, Settembre EC, Cirillo A, Pandit S, Ni YG, Hubbard B, Sitlani A, Carfi A. Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. 2011 Dec 1;12(12):1300-5. doi: 10.1038/embor.2011.205. PMID:22081141 doi:
  16. 16.0 16.1 Giunzioni I, Tavori H. New developments in atherosclerosis: clinical potential of PCSK9 inhibition. Vasc Health Risk Manag. 2015 Aug 24;11:493-501. doi: 10.2147/VHRM.S74692., eCollection 2015. PMID:26345307 doi:
  17. 17.0 17.1 17.2 17.3 17.4 17.5 El Khoury P, Elbitar S, Ghaleb Y, Khalil YA, Varret M, Boileau C, Abifadel M. PCSK9 Mutations in Familial Hypercholesterolemia: from a Groundbreaking Discovery to Anti-PCSK9 Therapies. Curr Atheroscler Rep. 2017 Oct 17;19(12):49. doi: 10.1007/s11883-017-0684-8. PMID:29038906 doi:
  18. 18.0 18.1 Zhang Y, Ultsch M, Skelton NJ, Burdick DJ, Beresini MH, Li W, Kong-Beltran M, Peterson A, Quinn J, Chiu C, Wu Y, Shia S, Moran P, Di Lello P, Eigenbrot C, Kirchhofer D. Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists. Nat Struct Mol Biol. 2017 Aug 21. doi: 10.1038/nsmb.3453. PMID:28825733 doi:
  19. Mitchell T, Chao G, Sitkoff D, Lo F, Monshizadegan H, Meyers D, Low S, Russo K, DiBella R, Denhez F, Gao M, Myers J, Duke G, Witmer M, Miao B, Ho SP, Khan J, Parker RA. Pharmacologic Profile of the Adnectin BMS-962476, a Small Protein Biologic Alternative to PCSK9 Antibodies for LDL Lowering. J Pharmacol Exp Ther. 2014 Jun 10. pii: jpet.114.214221. PMID:24917546 doi:
  20. Mullard A. Nine paths to PCSK9 inhibition. Nat Rev Drug Discov. 2017 Apr 28;16(5):299-301. doi: 10.1038/nrd.2017.83. PMID:28450722 doi:

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