PCSK9 Prosegment Chimera as Novel Inhibitors of LDLR Degradation

PLoS ONE

Volumn 8, Issue 8, 2013, Pages

  Luna Saavedra, Yascara Grisel ^a   Zhang, Jianbing ^b   Seidah, Nabil G ^a  

^a CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^b NATIONAL RESEARCH COUNCIL CANADA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN G1; LOW DENSITY LIPOPROTEIN RECEPTOR; PCSK9 INHIBITOR; PROTEINASE INHIBITOR; RECOMBINANT FCPRO PROTEIN; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL STRAIN HEK293; CELL STRAIN HEPG2; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; HUMAN; HUMAN CELL; IN VITRO STUDY; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN SECRETION;

EXTRACELLULAR SPACE; GENE EXPRESSION; HEK293 CELLS; HEP G2 CELLS; HUMANS; IMMUNOGLOBULIN FC FRAGMENTS; IMMUNOGLOBULIN G; MUTATION; PROPROTEIN CONVERTASES; PROTEIN BINDING; PROTEOLYSIS; RECEPTORS, LDL; RECOMBINANT FUSION PROTEINS; SERINE ENDOPEPTIDASES;

EID: 84881538945     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0072113     Document Type: Article

References (33)

1. Seidah NG, Prat A, (2012) The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov 11: 367-383.
2. Shinde U, Thomas G, (2011) Insights from bacterial subtilases into the mechanisms of intramolecular chaperone-mediated activation of furin. Methods Mol Biol 768: 59-106.
3. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, et al. (2003) The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A 100: 928-933.
4. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, et al. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34: 154-156.
5. Cunningham D, Danley DE, Geoghegan KF, Griffor MC, Hawkins JL, et al. (2007) Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol 14: 413-419.
6. Piper DE, Jackson S, Liu Q, Romanow WG, Shetterly S, et al. (2007) The Crystal Structure of PCSK9: A Regulator of Plasma LDL-Cholesterol. Structure 15: 545-552.
7. Hampton EN, Knuth MW, Li J, Harris JL, Lesley SA, et al. (2007) The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain. Proc Natl Acad Sci U S A 104: 14604-14609.
8. Zhang DW, Lagace TA, Garuti R, Zhao Z, McDonald M, et al. (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: 18602-18612.
9. Poirier S, Mayer G, Poupon V, McPherson PS, Desjardins R, et al. (2009) Dissection of the endogenous cellular pathways of PCSK9-induced LDLR degradation: Evidence for an intracellular route. J Biol Chem 284: 28856-28864.
10. Cameron J, Holla OL, Ranheim T, Kulseth MA, Berge KE, et al. (2006) Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 15: 1551-1558.
11. Benjannet S, Rhainds D, Essalmani R, Mayne J, Wickham L, et al. (2004) NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem 279: 48865-48875.
12. Nassoury N, Blasiole DA, Tebon OA, Benjannet S, Hamelin J, et al. (2007) The Cellular Trafficking of the Secretory Proprotein Convertase PCSK9 and Its Dependence on the LDLR. Traffic 8: 718-732.
13. Cariou B, Le MC, Costet P, (2011) Clinical aspects of PCSK9. Atherosclerosis 216: 258-265.
14. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, et al. (2005) Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37: 161-165.
15. Seidah NG, Mayer G, Zaid A, Rousselet E, Nassoury N, et al. (2008) The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol 40: 1111-1125.
16. Saavedra YG, Day R, Seidah NG, (2012) The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 is needed for the extracellular low density lipoprotein receptor (LDLR) degradation pathway. J Biol Chem 287: 43492-43501.
17. Zhang J, Liu X, Bell A, To R, Baral TN, et al. (2009) Transient expression and purification of chimeric heavy chain antibodies. Protein Expr Purif 65: 77-82.
18. Benjannet S, Saavedra YG, Hamelin J, Asselin MC, Essalmani R, et al. (2010) Effects of the prosegment and pH on the activity of PCSK9: evidence for additional processing events. J Biol Chem 285: 40965-40978.
19. Lo KM, Sudo Y, Chen J, Li Y, Lan Y, et al. (1998) High level expression and secretion of Fc-X fusion proteins in mammalian cells. Protein Eng 11: 495-500.
20. Zaid A, Roubtsova A, Essalmani R, Marcinkiewicz J, Chamberland A, et al. (2008) Proprotein convertase subtilisin/kexin type 9 (PCSK9): Hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology 48: 646-654.
21. Roubtsova A, Munkonda MN, Awan Z, Marcinkiewicz J, Chamberland A, et al. (2011) Circulating Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Regulates VLDLR Protein and Triglyceride Accumulation in Visceral Adipose Tissue. Arterioscler Thromb Vasc Biol 31: 785-791.
22. Zhong M, Munzer JS, Basak A, Benjannet S, Mowla SJ, et al. (1999) The prosegments of furin and PC7 as potent inhibitors of proprotein convertases. In vitro and ex vivo assessment of their efficacy and selectivity. J Biol Chem 274: 33913-33920.
23. Benjannet S, Hamelin J, Chretien M, Seidah NG, (2012) Loss- and Gain-of-function PCSK9 Variants: Clevage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation. J Biol Chem 287: 33745-33755.
24. Mayne J, Dewpura T, Raymond A, Bernier L, Cousins M, et al. (2011) Novel Loss-of-Function PCSK9 Variant Is Associated with Low Plasma LDL Cholesterol in a French-Canadian Family and with Impaired Processing and Secretion in Cell Culture. Clin Chem 57: 1415-1423.
25. Boudreault A, Gauthier D, Lazure C, (1998) Proprotein convertase PC1/3-related peptides are potent slow tight- binding inhibitors of murine PC1/3 and Hfurin. J Biol Chem 273: 31574-31580.
26. Nour N, Mayer G, Mort JS, Salvas A, Mbikay M, et al. (2005) The Cysteine-rich Domain of the Secreted Proprotein Convertases PC5A and PACE4 Functions as a Cell Surface Anchor and Interacts with Tissue Inhibitors of Metalloproteinases. Mol Biol Cell 16: 5215-5226.
27. Pullikotil P, Vincent M, Nichol ST, Seidah NG, (2004) Development of protein-based inhibitors of the proprotein of convertase SKI-1/S1P: processing of SREBP-2, ATF6, and a viral glycoprotein. J Biol Chem 279: 17338-17347.
28. Carter PJ, (2011) Introduction to current and future protein therapeutics: a protein engineering perspective. Exp Cell Res 317: 1261-1269.
29. Walsh G, (2010) Biopharmaceutical benchmarks 2010. Nat Biotechnol 28: 917-924.
30. Seidah NG, (2013) Proprotein Convertase Subtilisin Kexin 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia and other pathologies. Curr Pharm Des 19: 3161-3172.
31. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, et al. (2012) Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med 366: 1108-1118.
32. Ying T, Chen W, Gong R, Feng Y, Dimitrov DS, (2012) Soluble monomeric IgG1 Fc. J Biol Chem 287: 19399-19408.
33. Sun X, Essalmani R, Day R, Khatib AM, Seidah NG, et al. (2012) Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver. Neoplasia 14: 1122-1131.