Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells

Atherosclerosis

Volumn 203, Issue 1, 2009, Pages 166-171

  Fasano, Tommaso ^a   Sun, Xi Ming ^a   Patel, Dilipkumar D ^a   Soutar, Anne K ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

EBV lymphocytes; FACS; Familial hypercholesterolaemia

Indexed keywords

ASPARTIC ACID; CELL SURFACE PROTEIN; CHOLESTEROL; GENE PRODUCT; GLUTAMIC ACID; LOW DENSITY LIPOPROTEIN RECEPTOR; MUTANT PROTEIN; PROTEIN PCSK9; TUBULIN; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ARTICLE; ATHEROSCLEROSIS; CELL IMMORTALIZATION; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; ENZYME ACTIVITY; FAMILIAL HYPERCHOLESTEROLEMIA; GENE; GENE MUTATION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; INTERNALIZATION; ISCHEMIC HEART DISEASE; MUTANT; PCSK9 GENE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN SECRETION; WILD TYPE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; CATALYSIS; CELL LINE; CELL SEPARATION; FLOW CYTOMETRY; GLUTAMIC ACID; HUMANS; LYMPHOCYTES; MODELS, BIOLOGICAL; MUTAGENESIS; MUTATION; RECEPTORS, LDL; SERINE ENDOPEPTIDASES; TIME FACTORS; TRANSFECTION;

EID: 60749122013     PISSN: 00219150     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2008.10.027     Document Type: Article

References (28)

1. Abifadel M., Varret M., Rabes J.P., et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34 (2003) 154-156
2. Cohen J., Pertsemlidis A., Kotowski I.K., et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37 (2005) 161-165
3. Seidah N.G., Benjannet S., Wickham L., et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A 100 (2003) 928-933
4. Maxwell K.N., Soccio R.E., Duncan E.M., Sehayek E., and Breslow J.L. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res 44 (2003) 2109-2119
5. Horton J.D., Shah N.A., Warrington J.A., et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A 100 (2003) 12027-12032
6. Park S.W., Moon Y.A., and Horton J.D. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem 279 (2004) 50630-50638
7. Maxwell K.N., Fisher E.A., and Breslow J.L. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci U S A 102 (2005) 2069-2074
8. Lagace T.A., Curtis D.E., Garuti R., et al. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest 116 (2006) 2995-3005
9. Zhang D.W., Lagace T.A., Garuti R., et al. 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 (2007) 18602-18612
10. Kwon H.J., Lagace T.A., McNutt M.C., Horton J.D., and Deisenhofer J. Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A 105 (2008) 1820-1825
11. Rashid S., Curtis D.E., Garuti R., et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A 102 (2005) 5374-5379
12. Cohen J.C., Boerwinkle E., Mosley Jr. T.H., and Hobbs H.H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354 (2006) 1264-1272
13. Fasano T., Cefalu A.B., Di Leo E., et al. A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol 27 (2007) 677-681
14. Naoumova R.P., Tosi I., Patel D., et al. Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response. Arterioscler Thromb Vasc Biol 25 (2005) 2654-2660
15. Cunningham D., Danley D.E., Geoghegan K.F., et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol 14 (2007) 413-419
16. Cameron J., Holla O.L., Ranheim T., et al. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 15 (2006) 1551-1558
17. Homer V.M., Marais A.D., Charlton F., et al. Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 196 (2008) 659-666
18. Pandit S., Wisniewski D., Santoro J.C., et al. Functional analysis of sites within PCSK9 responsible for hypercholesterolemia. J Lipid Res 49 (2008) 1333-1343
19. Bourbon M., Alves A.C., Medeiros A.M., Silva S., and Soutar A.K. Familial hypercholesterolaemia in Portugal. Atherosclerosis 196 (2008) 633-642
20. Pisciotta L., Priore Oliva C., Cefalu A.B., et al. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis 186 (2006) 433-440
21. Eden E.R., Patel D.D., Sun X.M., et al. Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1. J Clin Invest 110 (2002) 1695-1702
22. Norman D., Sun X.M., Bourbon M., et al. Characterization of a novel cellular defect in patients with phenotypic homozygous familial hypercholesterolemia. J Clin Invest 104 (1999) 619-628
23. Sun X.M., Eden E.R., Tosi I., et al. Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia. Hum Mol Genet 14 (2005) 1161-1169
24. Horton J.D., Cohen J.C., and Hobbs H.H. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem Sci 32 (2007) 71-77
25. Hampton E.N., Knuth M.W., Li J., et al. 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 (2007) 14604-14609
26. Michaely P., Zhao Z., Li W.P., et al. Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR. EMBO J 26 (2007) 3273-3282
27. Holla Ø.L., Cameron J., Berge K.E., Ranheim T., and Leren T.P. Degradation of the LDL receptors by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly. BMC Cell Biol 8 (2007) 9
28. Grefhorst A., McNutt M.C., Lagace T.A., and Horton J.D. Plasma PCSK9 preferentially reduces liver LDL receptors in mice. J Lipid Res 49 (2008) 1303-1311