Functional Consequences of a Novel Variant of PCSK1

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Pickett, Lindsay A ^b   Yourshaw, Michael ^a   Albornoz, Valeria ^b   Chen, Zijun ^a   Solorzano Vargas, R Sergio ^a   Nelson, Stanley F ^a   Martín, Martín G ^a   Lindberg, Iris ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; GLUTAMINE; PROPROTEIN CONVERTASE 1;

AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME RELEASE; ENZYME SYNTHESIS; FEMALE; GENE; GENE FREQUENCY; GENE FUNCTION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HUMAN; IN VITRO STUDY; NUCLEOTIDE SEQUENCE; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 1 GENE; PROTEIN EXPRESSION; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; STRUCTURE ACTIVITY RELATION; TRANSIENT TRANSFECTION; VALIDATION PROCESS; WESTERN BLOTTING; WILD TYPE;

BIOCATALYSIS; DATABASES, GENETIC; DIABETES MELLITUS; FEMALE; HUMANS; NEUROPEPTIDES; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; SEQUENCE ANALYSIS, DNA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84873801109     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0055065     Document Type: Article

References (54)

1. Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, et al. (1991) Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region). Genomics 11: 103-107.
2. Hoshino A, Lindberg I (2012) Peptide Biosynthesis: Prohormone Convertases 1/3 and 2. In: Fricker LD, Devi L, editors: Morgan & Claypool Life Sciences Publishers.
3. Schafer MK, Day R, Cullinan WE, Chretien M, Seidah NG, et al. (1993) Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis. J Neurosci 13: 1258-1279.
4. Dong W, Seidel B, Marcinkiewicz M, Chretien M, Seidah NG, et al. (1997) Cellular localization of the prohormone convertases in the hypothalamic paraventricular and supraoptic nuclei: selective regulation of PC1 in corticotrophin-releasing hormone parvocellular neurons mediated by glucocorticoids. J Neurosci 17: 563-575.
5. Wynne K, Stanley S, McGowan B, Bloom S, (2005) Appetite control. J Endocrinol 184: 291-318.
6. Smeekens S, Montag AG, Thomas G, Albiges-Rizo C, Carrol R, et al. (1992) Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3. Proc Natl Acad Sci USA 89: 8822-8826.
7. Rouille Y, Kantengwa S, Irminger JC, Halban PA, (1997) Role of the prohormone convertases in the processing of proglucagon to glucagon-like peptides. J Biol Chem 72: 32810-32816.
8. Zhu X, Zhou A, Dey A, Norrbom C, Carroll R, et al. (2002) Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proc Natl Acad Sci USA 99: 10293-10298.
9. Zhu X, Cao Y, Voogd K, Steiner DF, (2006) On the processing of proghrelin to ghrelin. J Biol Chem 281: 38867-38870.
10. Creemers JW, Pritchard LE, Gyte A, Le Rouzic P, Meulemans S, et al. (2006) Agouti-related protein is posttranslationally cleaved by proprotein convertase 1 to generate agouti-related protein (AGRP)83-132: interaction between AGRP83-132 and melanocortin receptors cannot be influenced by syndecan-3. Endocrinology 147: 1621-1631.
11. Brakch N, Rist B, Beck-Sickinger AG, Goenaga J, Wittek R, et al. (1997) Role of prohormone convertases in pro-neuropeptide Y processing: coexpression and in vitro kinetic investigations. Biochemistry 36: 16309-16320.
12. Coates LC, Birch NP, (1998) Differential cleavage of provasopressin by the major molecular forms of SPC3. J Neurochem 70: 1670-1678.
13. Benjannet S, Rondeau N, Day R, Chretien M, Seidah NG, (1991) PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues. Proc Natl Acad Sci U S A 88: 3564-3568.
14. Thomas L, Leduc R, Thorne BA, Smeekens SP, Steiner D, et al. (1991) Kex2-like endoproteases PC2 and PC3 accurately cleave a model prohormone in mammalian cells: evidence for a common core of neuroendocrine processing enzymes. Proc Natl Acad Sci USA 88: 5297-5301.
15. Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A, et al. (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 112: 1550-1560.
16. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, et al. (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16: 303-306.
17. Farooqi IS, Volders K, Stanhope R, Heuschkel R, White A, et al. (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 92: 3369-3373.
18. Lloyd DJ, Bohan S, Gekakis N, (2006) Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice. Hum Mol Genet 15: 1884-1893.
19. Mbikay M, Sirois F, Nkongolo KK, Basak A, Chretien M, (2011) Effects of rs6234/rs6235 and rs6232/rs6234/rs6235 PCSK1 single-nucleotide polymorphism clusters on proprotein convertase 1/3 biosynthesis and activity. Mol Genet Metab 104: 682-687.
20. Benzinou M, Creemers JW, Choquet H, Lobbens S, Dina C, et al. (2008) Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet 40: 943-945.
21. Strawbridge RJ, Dupuis J, Prokopenko I, Barker A, Ahlqvist E, et al. (2011) Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes 60: 2624-2634.
22. Heni M, Haupt A, Schafer SA, Ketterer C, Thamer C, et al. (2010) Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion. BMC Med Genet 11: 86.
23. Finishing the euchromatic sequence of the human genome. Nature 431: 931-945.
24. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, et al. (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29: 308-311.
25. A map of human genome variation from population-scale sequencing. Nature 467: 1061-1073.
26. NHLBI Exome Sequencing Project (2011) Exome Variant Server. Seattle WA: NHLBI Exome Sequencing Project (ESP).
27. NIEHS Environmental Genome Project (2011) NIEHS Exome Variant Server. Seattle WA: NIEHS Environmental Genome Project.
28. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, et al. (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297-1303.
29. Flicek P, Amode MR, Barrell D, Beal K, Brent S, et al. (2011) Ensembl 2011. Nucleic Acids Res 39: D800-806.
30. Kumar P, Henikoff S, Ng PC, (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nature Protocols 4: 1073-1082.
31. Ng PC, Henikoff S, (2002) Accounting for human polymorphisms predicted to affect protein function. Genome Research 12: 436-446.
32. Ng CP, Henikoff S, (2003) SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Research 31: 3812-3814.
33. Ng PC, Henikoff S, (2006) Predicting the effects of amino acid substitutions on protein function. Annual Review of Genomics and Human Genetics 7: 61-80.
34. Ramensky V, Bork P, Sunyaev S, (2002) Human non-synonymous SNPs: server and survey. Nucleic Acids Res 30: 3894-3900.
35. Sunyaev S, Ramensky V, Bork P, (2000) Towards a structural basis of human non-synonymous single nucleotide polymorphisms. Trends Genet 16: 198-200.
36. Sunyaev S, Ramensky V, Koch I, Lathe W 3rd, Kondrashov AS, et al. (2001) Prediction of deleterious human alleles. Human Molecular Genetics 10: 591-597.
37. Gonzalez-Perez A, Lopez-Bigas N, (2011) Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. American Journal of Human Genetics 88: 440-449.
38. Braman J, Papworth C, Greener A, (1996) Site-directed mutagenesis using double-stranded plasmid DNA templates. Methods Mol Biol 57: 31-44.
39. Vindrola O, Lindberg I, (1992) Biosynthesis of the prohormone convertase mPC1 in AtT-20 cells. Mol Endocrinol 6: 1088-1094.
40. Creemers JW, Choquet H, Stijnen P, Vatin V, Pigeyre M, et al. (2012) Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity. Diabetes 61: 383-390.
41. Zhou Y, Rovere C, Kitabgi P, Lindberg I, (1995) Mutational analysis of PC1 (SPC3) in PC12 cells. 66-kDa PC1 is fully functional. J Biol Chem 270: 24702-24706.
42. Zhou A, Mains RE, (1994) Endoproteolytic processing of proopiomelanocortin and prohormone convertases 1 and 2 in neuroendocrine cells overexpressing prohormone convertases 1 or 2. J Biol Chem 269: 17440-17447.
43. Bernard N, Kitabgi P, Rovere-Jovene C, (2003) The Arg617-Arg618 cleavage site in the C-terminal domain of PC1 plays a major role in the processing and targeting of the enzyme within the regulated secretory pathway. J Neurochem 85: 1592-1603.
44. Rabah N, Gauthier D, Wilkes BC, Gauthier DJ, Lazure C, (2006) Single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzyme. J Biol Chem 281: 7556-7567.
45. Goodman LJ, Gorman CM, (1994) Autoproteolytic activation of the mouse prohormone convertase mPC1. Biochem Biophys Res Commun 201: 795-804.
46. Anderson ED, VanSlyke JK, Thulin CD, Jean F, Thomas G, (1997) Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage. EMBO J 16: 1508-1518.
47. Creemers JW, Vey M, Schafer W, Ayoubi TA, Roebroek AJ, et al. (1995) Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum. J Biol Chem 270: 2695-2702.
48. Mains RE, Milgram SL, Keutman HT, Eipper BA, (1995) The NH2-terminal proregion of peptidylglycine a-amidating monooxygenase facilitates the secretion of soluble proteins. Mol Endocrinol 9: 3-13.
49. Apletalina EV, Juliano MA, Juliano L, Lindberg I, (2000) Structure-function analysis of the 7B2 CT peptide. Biochem Biophys Res Commun 267: 940-942.
50. Muller L, Cameron A, Fortenberry Y, Apletalina EV, Lindberg I, (2000) Processing and sorting of the prohormone convertase 2 propeptide. J Biol Chem 275: 39213-39222.
51. Bissonnette L, Charest G, Longpre JM, Lavigne P, Leduc R, (2004) Identification of furin pro-region determinants involved in folding and activation. Biochem J 379: 757-763.
52. Lee SN, Prodhomme E, Lindberg I, (2004) Prohormone convertase 1 (PC1) processing and sorting: effect of PC1 propeptide and proSAAS. J Endocrinol 182: 353-364.
53. Tangrea MA, Bryan PN, Sari N, Orban J, (2002) Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus. J Mol Biol 320: 801-812.
54. Benjannet S, Rondeau N, Paquet L, Boudreault A, Lazure C, et al. (1993) Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2. Biochem J 294 (Pt 3) (): 735-743.