Regulation of prohepcidin processing and activity by the subtilisin-like proprotein convertases Furin, PC5, PACE4 and PC7

Gut

Volumn 57, Issue 11, 2008, Pages 1573-1582

  Scamuffa, N ^a   Basak, A ^b   Lalou, C ^a   Wargnier, A ^c   Marcinkiewicz, J ^d   Siegfried, G ^e   Chretien M ^b   Calvo, F ^a   Seidah, N G ^d   Khatib, A M ^a  

^a INSERM   (France)

^b OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^c SAINT LOUIS HOSPITAL   (France)

^d CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^e UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA 1 ANTITRYPSIN; FERROPORTIN; FURIN; HEPCIDIN; HORMONE PRECURSOR; PAIRED BASIC AMINO ACID CLEAVING ENZYME 4; PREPROFURIN; PROHEPCIDIN; PROPROTEIN CONVERTASE 5; PROPROTEIN CONVERTASE 7; SERINE PROTEINASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CELL LINE; CONTROLLED STUDY; EMBRYO; ENZYME ACTIVITY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN MOTIF; PROTEIN PROCESSING; SITE DIRECTED MUTAGENESIS;

ALPHA 1-ANTITRYPSIN; ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; CATION TRANSPORT PROTEINS; CELL LINE; FURIN; HUMANS; LIVER; MICE; MUTAGENESIS, SITE-DIRECTED; NEOPLASMS; PROPROTEIN CONVERTASE 5; PROPROTEIN CONVERTASES; SERINE ENDOPEPTIDASES; TRANSFECTION;

EID: 54349122894     PISSN: 00175749     EISSN: None     Source Type: Journal    
DOI: 10.1136/gut.2007.141812     Document Type: Article

References (46)

1. Krause A, Neitz S, Magert HJ, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000;480:147-50.
2. Park CH, Valore EV, Waring AJ, et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806-10.
3. Ganz T. Hepcidin. A key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783-8.
4. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001;276:7811-9.
5. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A 2001;98:8780-5.
6. Vallet VS, Casado M, Henrion AA, et al. Differential roles of upstream stimulatory factors 1 and 2 in the transcriptional response of liver genes to glucose. J Biol Chem 1998;273:20175-9.
7. Fleming RE, Sly WS. Mechanisms of iron accumulation in hereditary hemochromatosis. Annu Rev Physiol 2002;64:663-80.
8. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-3.
9. De Domenico I, Ward DM, Langelier C, et al. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 2007;18:2569-78.
10. Kulaksiz H, Gehrke SG, Janetzko A, et al. Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia. Gut 2004;53:735-43.
11. Wallace DF, Summerville L, Lusby PE, et al. Prohepcidin localises to the Golgi compartment and secretory pathway in hepatocytes. J Hepatol 2005;43:720-8.
12. Molloy SS, Anderson ED, Jean F, et al. Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis. Trends Cell Biol 1999;9:28-35.
13. Valore EV, Ganz T. Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells Mol Dis 2008;40:132-8.
14. Khatib AM, Siegfried G, Chretien M, et al. Proprotein convertases in tumor progression and malignancy: novel targets in cancer therapy. Am J Pathol 2002;160:1921-35.
15. Nakayama K. Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochem J 1997;327:625-35.
16. Zhou A, Webb G, Zhu X, et al. Proteolytic processing in the secretory pathway. J Biol Chem 1999;274:20745-8.
17. Seidah NG, Chretien M. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res 1999;848:45-62.
18. Bergeron E, Basak A, Decroly E, et al. Processing of alpha4 integrin by the proprotein convertases: histidine at position P6 regulates cleavage. Biochem J 2003;373:475-84.
19. Siegfried G, Basak A, Prichett-Pejic W, et al. Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases. Oncogene 2005;24:6925-35.
20. Siegfried G, Basak A, Cromlish JA, et al. The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis. J Clin Invest 2003;111:1723-32.
21. Jin W, Fuki IV, Seidah NG, et al. Proprotein covertases are responsible for proteolysis and inactivation of endothelial lipase. J Biol Chem 2005;280:36551-9.
22. Fukumoto S. Post-translational modification of fibroblast growth factor 23. Ther Apher Dial 2005;9:319-22.
23. Cao J, Rehemtulla A, Pavlaki M, et al. Furin directly cleaves proMMP-2 in the trans-golgi network resulting in a non-functioning proteinase. J Biol Chem 2005;280:10974-80.
24. Lee R, Kermani P, Teng KK, et al. Regulation of cell survival by secreted proneurotrophins. Science 2001;294:1945-6.
25. Zhong M, Munzer JS, Basak A, et al. 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 1999;274:33913-20.
26. Anderson ED, Thomas L, Hayflick JS, et al. Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant. J Biol Chem 1993;268:24887-91.
27. Takahashi S, Kasai K, Hatsuzawa K, et al. A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells. Biochem Biophys Res Commun 1993;195:1019-26.
28. Ward DG, Roberts K, Brookes MJ, et al. Increased hepcidin expression in colorectal carcinogenesis. World J Gastroenterol 2008;14:1339-45.
29. Essalmani R, Hamelin J, Marcinkiewicz J, et al. Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse. Mol Cell Biol 2006;26:354-61.
30. Jean F, Basak A, Rondeau N, et al. Enzymic characterization of murine and human prohormone convertase-1 (mPC1 and hPC1) expressed in mammalian GH4C1 cells. Biochem J 1993;292:891-900.
31. Courselaud B, Troadec MB, Fruchon S, et al. Strain and gender modulate hepatic hepcidin 1 and 2 mRNA expression in mice. Blood Cells Mol Dis 2004;32:283-9.
32. Creemers WM, Khatib AM. Knock-out mouse models of proprotein convertases: unique functions or redundancy? Frontiers in Bioscience 2008;13:4960-71. http://www.bioscience.org/2008/v13/af/3055/fulltext.htm (accessed 18 August 2008).
33. Stawowy P, Meyborg H, Stibenz D, et al. Furin-like proprotein convertases are central regulators of the membrane type matrix metalloproteinase-pro-matrix metalloproteinase-2 proteolytic cascade in atherosclerosis. Circulation 2005;111:2820-7.
34. Roebroek AJ, Taylor NA, Louagie E, et al. Limited redundancy of the proprotein convertase furin in mouse liver. J Biol Chem 2004;279:53442-50.
35. Hsu SP, Chiang CK, Chien CT, et al. Plasma prohepcidin positively correlates with hematocrit in chronic hemodialysis patients. Blood Purif 2006;24:311-6.
36. Nour N, Mayer G, Mort JS, et al. 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 2005;16:5215-26.
37. Nemeth E, Preza GC, Jung CL, et al. The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 2006;107:328-33.
38. Pietrangalo A. Hemochromatosis: an endocrine liver disease. Hepatology 2007;46:1291-301.
39. Roetto A, Papanikolaou G, Politou M, et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 2003;33:21-2.
40. Nemeth E, Valore EV, Territo M, et al. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003;101:2461-3.
41. Weinstein DA, Roy CN, Fleming MD, et al. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 2002;100:3776-81.
42. Brookes MJ, Hughes S, Turner FE, et al. Modulation of iron transport proteins in human colorectal carcinogenesis. Gut 2006;55:1384-6.
43. Peeling P, Dawson B, Goodman C, et al. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol Published Online First. doi: 10.1007/S00421-008-0726-6.
44. Scamuffa N, Siegfried G, Bontemps Y, et al. Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells. J Clin Invest 2008;118:352-63.
45. Folgueras AR, Martin de Lara F, Pendas AM, et al. The membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood Published Online First. doi: 10.1182/blood-2008-04-149773.
46. Finberg KE, Heeney MM, Campagna DR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008;40:569-71.