Cystatins in immune system

Journal of Cancer

Volumn 4, Issue 1, 2013, Pages 45-56

  Magister, Špela ^a   Kos, Janko ^a,b  

^a JO EF STEFAN INSTITUTE   (Slovenia)

^b UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

Cathepsin; Cystatin; Disease; Immune cells; Inhibitor; Protease; Proteolytic activity; Stefin; Tumor

Indexed keywords

CATHEPSIN; CYSTATIN; CYSTATIN B; CYSTATIN C; CYSTATIN F; CYSTATIN M; UNCLASSIFIED DRUG;

CARCINOGENESIS; CELL MATURATION; CELL PROLIFERATION; DENDRITIC CELL; EPITHELIUM; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; LYSOSOME; METASTASIS; NATURAL KILLER CELL; PROTEIN EXPRESSION; REVIEW; TUMOR IMMUNOLOGY; TUMOR INVASION;

EID: 84881288420     PISSN: None     EISSN: 18379664     Source Type: Journal    
DOI: 10.7150/jca.5044     Document Type: Review

References (159)

1. Barrett AJ, Rawlings ND, Woessner JF: The Handbook of Proteolytic Enzymes. Academic Press, 2004.
2. Honey K, Rudensky AY: Lysosomal cysteine proteases regulate antigen presentation. Nat Rev Immunol 2003; 3:472-482.
3. Chapman HA, Riese RJ, Shi GP: Emerging roles for cysteine proteases in human biology. Annu Rev Physiol 1997; 59:63-88.
4. Turk B, Turk D, Salvesen GS: Regulating cysteine protease activity: essential role of protease inhibitors as guardians and regulators. Curr Pharm Des 2002; 8:1623-1637.
5. Turk V , Turk B , Turk D : L ysosomal c ysteine p roteases: f acts a nd opportunities. EMBO J 2001; 20:4629-4633.
6. Kos J, Werle B, Lah T, Brunner N: Cysteine proteases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. Int J Biol Markers 2000; 15:84-89.
7. Lang A, Horler D, Baici A: The relative importance of cysteine peptidases in osteoarthritis. J Rheumatol 2000; 27:1970-1979.
8. Felbor U, Kessler B, Mothes W, Goebel HH, Ploegh HL, Bronson RT, Olsen BR: Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc Natl Acad Sci U S A 2002; 99:7883-7888.
9. Kos J, Lah TT: Cysteine proteases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). Oncol Rep 1998; 5:1349-13461.
10. Levicar N, Kos J, Blejec A, Golouh R, Vrhovec I, Frkovic-Grazio S, Lah T: Comparison of potential biological markers cathepsin B, cathepsin L, stefin A and stefin B with urokinase and plasminogen activator inhibitor-1 and clinicopathological data of breast carcinoma patients. Cancer Det Prev 2002; 26:42-49.
11. Berdowska I: Cysteine proteases as disease markers. Clin Chim Acta 2004; 342:41-69.
12. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E , T sai F Y: Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 2004; 5:443-453.
13. Rawlings ND, Barrett AJ: Evolution of proteins of the cystatin superfamily. J Mol Evol 1990; 30:60-71.
14. Abrahamson M: Cystatins. Methods Enzymol 1994; 244:685-700.
15. Keppler D: Towards novel anti-cancer strategies based on cystatin function. Cancer Lett 2005; 235:159-176.
16. Henskens YMC, Veerman ECI, Amerongen AVN: Cystatins in health and diseases. Biol Chem Hoppe-Seyler 1996; 377:71-86.
17. Pierre P, Mellman I: Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 1998; 93:1135-1145.
18. Calkins CC, Sloane BF: Mammalian cysteine peptidase inhibitors: biochemical properties and possible roles in tumor progression. Biol Chem 1995; 376:71-80.
19. Machleidt W, Borchart U, Fritz H, Brzin J, Ritonja A, Turk V: Protein inhibitors of cysteine proteinases. II. Primary structure of stefin, a cytosolic protein inhibitor of cysteine proteinases from human polymorphonuclear granulocytes. Hoppe Seylers Z Physiol Chem 1983; 364:1481-1486.
20. Ritonja A, Machleidt W, Barrett AJ: Amino acid sequence of the intracellular cysteine proteinase inhibitor cystatin B from human liver. Biochem Biophys Res Commun 1985; 131:1187-1192.
21. Stubbs MT, Laber B, Bode W, Huber R, Jerala R, Lenarcic B, Turk V: The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction. EMBO J 1990; 9:1939-1947.
22. Jenko S, Dolenc I, Guncar G, Doberšek A, Podobnik M, Turk D: Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases. J Mol Biol 2003; 326:875-885.
23. Jenko S, Škarabot M, Kenig M, Guncar G, Muševic I, Turk D, Žerovnik E: Different propensity to form amyloid fibrils by two homologous proteins-human stefins A and B: searching for an explanation. Proteins 2004; 55:417-425.
24. Jenko Kokalj S, Guncar G, Štern I, Morgan G, Rabzelj S, Kenig M, Staniforth RA, Waltho JP, Žerovnik E, Turk D: Essential role of proline isomerization in stefin B tetramer formation. J Mol Biol 2007; 366:1569-1579.
25. Smajlovic A, Berbic S, Schiene-Fischer C, Tušek-Žnidaric M, Taler A, Jenko-Kokalj S, Turk D, Žerovnik E: Essential role of Pro 74 in stefin B amyloid-fibril formation: dual action of cyclophilin A on the process. FEBS Lett 2009; 583:1114-1120.
26. Järvinen M, Hopsu-Havu VK: Alpha-N-benzoylarginine-2- naphthylamide hydrolase (cathepsin B1?) from rat skin. I. Preliminary experiments with skin extract. Acta Chem Scand B 1975; 29:671-676.
27. Rinne A: Epidermal SH-protease inhibitor in human neoplasms and their metastases. Pathol Res Pract 1980; 170:172-179.
28. Järvinen M, Pernu H, Rinne A, Hopsu-Havu VK, Altonen M: Localization of three inhibitors of cysteineproteinases in the human oral mucosa. Acta Histochem 1983; 73:279-282.
29. Rinne A, Järvinen M, Rasanen O: A protein reminiscent of the epidermal SH-protease inhibitor occurs in squamous epithelia of man and rat. Acta Histochem 1978; 63:183-192.
30. Räsänen O, Järvinen M, Rinne A: Localization of the human SH-protease inhibitor in the epidermis. Immunofluorescent studies. Acta Histochem 1978; 63:193-196.
31. Söderström KO, Laato M, Wu P, Hopsu-Havu VK, Nurmi M, Rinne A: Expression of acid cysteine proteinase inhibitor (ACPI) in the normal human prostate, benign prostatic hyperplasia and adenocarcinoma. Int J Cancer 1995; 62:1-4.
32. Davies ME, Barrett AJ: Immunolocalization of human cystatins in neutrophils and lymphocytes. Histochemistry 1984; 80:373-377.
33. Rinne A, Alavaikko M, Järvinen M, Martikainen J, Karttunen T, Hopsu-Havu V: Demonstration of immunoreactive acid cysteine-proteinase inhibitor in reticulum cells of lymph node germinal centres. Virchows Arch B Cell Pathol Incl Mol Pathol 1983; 43:121-126.
34. Soderstrom KO, Rinne R, Hopsu-Havu VK, Järvinen M, Rinne A: Identification of acid cysteine proteinase inhibitor (cystatin A) in the human thymus. Anat Rec 1994; 240:115-119.
35. Scott DK, Lord R , Muller H K, Malley RC, Woods GM: P roteomics identifies enhanced expression of stefin A in neonatal murine skin compared with adults: functional implications. Br J Dermatol 2007; 156:1156-1162.
36. Järvinen M, Rinne A: Human spleen cysteine proteinase inhibitor. Purification, fractionation into isoelectric variants and some properties of the variants. Biochim Biophys Acta 1982; 708:210-217.
37. Hopsu-Havu VK, Joronen IA, Järvinen M, Rinne A, Aalto M: Cysteine proteinase inhibitors produced by mononuclear phagocytes. Cell Tissue Res 1984; 236:161-164.
38. Suzuki T, Hashimoto S, Toyoda N, Nagai S, Yamazaki N, Dong HY, Sakai J, Yamashita T, Nukiwa T, Matsushima K: Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE. Blood 2000; 96:2584-2591.
39. Riccio M, Di Giaimo R, Pianetti S, Palmieri PP, Melli M, Santi S: Nuclear localization of cystatin B, the cathepsin Inhibitor Implicated in myoclonus epilepsy (EPM1). Experimental Cell Research 2001; 262:84-94.
40. Ceru S, Konjar š, Maher K, Repnik U, Križaj I, Bencina M, Renko M, Nepveu A, Žerovnik E, Turk B, Kopitar-Jerala N: Stefin B Interacts with histones and cathepsin L in the nucleus. J Biol Chem 2010; 285:10078-10086.
41. Bowcock AM, Shannon W, Du F, Duncan J, Cao K, Aftergut K, Catier J, Fernandez-Vina MA, Menter A: Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies. Hum Mol Genet 2001; 10:1793-1805.
42. Vasilopoulos Y, Cork MJ, Teare D, Marinou I, Ward SJ, Duff GW, Tazi-Ahnini R: A nonsynonymous substitution of cystatin A, a cysteine protease inhibitor of house dust mite protease, leads to decreased mRNA stability and shows a significant association with atopic dermatitis. Allergy 2007; 62:514-519.
43. Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, Duff GW, Ward SJ, Tazi-Ahnini R: New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J Allergy Clin Immunol 2006; 118:3-21.
44. Ogawa T, Takai T, Kato T, Kikuchi Y, Niyonsaba F, Ikeda S, Okumura K, Ogawa H: Upregulation of the release of granulocyte-macrophage colony-stimulating factor from keratinocytes stimulated with cysteine protease activity of recombinant major mite allergens, Der f 1 and Der p 1. Int Arch Allergy Immunol 2008; 146:27-35.
45. Kato T, Takai T, Mitsuishi K, Okumura K, Ogawa H: Cystatin A inhibits IL-8 production by keratinocytes stimulated with Der p 1 and Der f 1: biochemical skin barrier against mite cysteine proteases. J Allergy Clin Immunol 2005; 116:169-176.
46. Blaydon DC, Nitoiu D , Eckl KM, Cabral R M, Bland P , H ausser I, van Heel DA, Rajpopat S, Fischer J, Oji V, Zvulunov A, Traupe H, Hennies HC, Kelsell DP: Mutations in CSTA, encoding cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet 2011; 89:564-571.
47. Di Giaimo R, Riccio M, Santi S, Galeotti C, Ambrosetti DC, Melli M: New insights into the molecular basis of progressive myoclonus epilepsy: amultiprotein complex with cystatin B. Hum Mol Genet 2002; 11:2941-2950.
48. Joensuu T, Lehesjoki AE, Kopra O: Molecular background of EPM1-Unverricht-Lundborg disease. Epilepsia 2008; 49:557-563.
49. Pennacchio LA, Lehesjoki AE, Stone NE, Willour VL, Virtaneva K, Miao J, D'Amato E , Ramirez L , Faham M , Koskiniemi M , Warrington JA, Norio R, de la Chapelle A, Cox DR, Myers RM: Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1). Science 1996; 271:1731-1734.
50. Lalioti MD, Mirotsou M, Buresi C, Peitsch MC, Rossier C, Ouazzani R, Baldy-Moulinier M, Bottani A, Malafosse A, Antonarakis SE: Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1). Am J Hum Genet 1997; 60:342-351.
51. Joensuu T , Kuronen M , Alakurtti K , Tegelberg S , Hakala P , Aalto A , Huopaniemi L, Aula N, Michellucci R, Eriksson K, Lehesjoki AE: Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients. Eur J Hum Genet 2007; 15:185-193.
52. Bespalova IN, Adkins S, Pranzatelli M, Burmeister M: Novel cystatin B mutation and diagnostic PCR assay in an Unverricht-Lundborg progressive myoclonus epilepsy patient. Am J Med Genet 1997; 74:467-471.
53. Alakurtti K, Weber E, Rinne R, Theil G, de Haan GJ, Lindhout D, Salmikangas P, Saukko P, Lahtinen U, Lehesjoki AE: Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations. Eur J Hum Genet 2005; 13:208-215.
54. Walsh DM, Selkoe DJ: Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration. Protein Pept Lett 2004; 11:213-228.
55. Žerovnik E: Amyloid-fibril formation. Proposed mechanisms and relevance to conformational disease, Eur J Biochem 2002; 269:3362-3371.
56. Levy E: Cystatin C: a potential target for Alzheimer's treatment. Expert Rev Neurother 2008; 8:687-689.
57. Škerget K, Taler-Vercic A, Bavdek A, Hodnik V, Ceru S, Tušek-Žnidaric M, Kumm T , Pitsi D , Pompe-Novak M, Palumaa P, Soriano S, Kopitar-Jerala N, Turk V, Anderluh G, Žerovnik E: Interaction between oligomers of stefin B and amyloid-beta in vitro and in cells. J Biol Chem 2010; 285:3201-3210.
58. Grubb A, Löfberg H: Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis. Proc Natl Acad Sci U S A 1982; 79:3024-3027.
59. Turk V, Brzin J, Longer M, Ritonja A, Eropkin M, Borchart U, Machleidt W: Protein inhibitors of cysteine proteinases. III. Amino-acid sequence of cystatin from chicken egg white. Hoppe Seylers Z Physiol Chem 1983; 364:1487-1496.
60. Abrahamson M , Grubb A , Olafsson I , Lundwall A : Molecular c loning and sequence analysis of cDNA coding for the precursor of the human cysteine proteinase inhibitor cystatin C. FEBS Lett 1987; 216:229-233.
61. Abrahamson M, Barrett AJ, Salvesen G, Grubb A: Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids. J Biol Chem 1986; 261:11282-11289.
62. Barrett AJ, Davies ME, Grubb A: The place of human γ-trace (cystatin C) amongst the cysteine proteinase inhibitors. Biochemical and Biophysical Research Communications 1984; 120:631-636.
63. Alvarez-Fernandez M, Barrett AJ, Gerhartz B, Dando PM, Ni J, Abrahamson M: Inhibition of mammalian legumain by some cystatins is due to a novel second reactive site. J Biol Chem 1999; 274:19195-19203.
64. Pierre P, Mellman I: Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 1998; 93:1135-1145.
65. El-Sukkari D, Wilson NS, Hakansson K, Steptoe RJ, Grubb A, Shortman K, Villadangos JA: The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation. J Immunol 2003; 171:5003-5011.
66. Zavašnik-Bergant T, Repnik U, Schweiger A, Romih R, Jeras M, Turk V, Kos J: Differentiation- and maturation-dependent content, localization, and secretion of cystatin C in human dendritic cells. J Leukoc Biol 2005; 78:122-134.
67. Magister š, Obermajer N , Mirkovic B, Švajger U, Renko M , Softic A, Romih R, Colbert JD, Watts C, Kos J: Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells. Eur J Cell Biol 2012; 91:391-401.
68. Halfon S, Ford J, Foster J, Dowling L, Lucian L, Sterling M, Xu Y, Weiss M, Ikeda M , Liggett D , Helms A , Caux C , Lebecque S, Hannum C, Menon S, McClanahan T, Gorman D, Zurawski G: Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells. J Biol Chem 1999; 273:16400-16408.
69. Ni J, Fernandez MA, Danielsson L, Chillakuru RA, Zhang J, Grubb A, Su J, Gentz R ,Abrahamson M : Cystatin Fisag lycosylated human low molecular weight cysteine proteinase inhibitor. J Biol Chem 1998; 273:24797-24804.
70. Morita M, Hara Y, Tamai Y, Arakawa H, Nishimura S: Genomic constructs and mapping of the gene for CMAP (leukocystatin/cystatin F, CST7) and identification of a proximal novel gene, BSCv (C20orf3). Genomics 2000; 67:87-91.
71. Cappello F, Gatti E, Camossetto V, David A, Lelouard H, Pierre P: Cystatin F is secreted, but artificial modification of its C-terminus can induce its endocytic targeting. Exp Cell Res 2004; 297:607-618.
72. Langerholc T, Zavasnik-Bergant V, Turk B, Turk V, Abrahamson M, Kos J: Inhibitory properties of cystatin F and its localization in U937 promonocyte cells. FEBS J 2005; 272:1535-1545.
73. Colbert JD, Plechanovova A, Watts C: Glycosylation directs targeting and activation of cystatin F from intracellular and extracellular sources. Traffic 2009; 10:425-437.
74. Schuttelkopf AW, Hamilton G, Watts C, van Aalten DM: Structural basis of reduction-dependent activation of human cystatin F. J Biol Chem 2006; 281:16570-16575.
75. Hamilton G, Colbert JD, Schuettelkopf AW, Watts C: Cystatin F is a cathepsin C-directed protease inhibitor regulated by proteolysis. EMBO J 2008; 27:499-508.
76. Langerholc T, Zavasnik-Bergant V, Turk B, Turk V, Abrahamson M, Kos J: Inhibitory properties of cystatin F and its localization in U937 promonocyte cells. FEBS J 2005; 272:1535-1545.
77. Hashimoto S-I, Suzuki T, Nagai S, Yamashita T, Toyoda N, Matsushima K: Identification of genes specifically expressed in human activated and mature dendritic cells through serial analysis of gene expression. Blood 2000; 96:2206-2214.
78. Obata-Onai A, Hashimoto S-I, Onai N, Kurachi M, Nagai S, Shizuno K-I, Nagahata T, Matsushima K: Comprehensive gene expression analysis of human NK cells and CD8+ T lymphocytes. Int Immunol 2002; 14:1085-1098.
79. Nathanson CM, Wassélius J, Wallin H, Abrahamson M: Regulated expression and intracellular localization of cystatin F in human U937 cells. Europ J Biochem 2002; 269:5502-5511.
80. Pham CT, Ley TJ: Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA 1999; 96:8627-8632.
81. Adkison AM, Raptis SZ, Kelley D G, Pham C T: Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J Clin Invest 2002; 109:363-371.
82. Sotiropoulou G, Anisowicz A, Sager R: Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer. J Biol Chem 1997; 272:903-910.
83. Ni J, Abrahamson M, Zhang M, Fernandez MA, Grubb A, Su J, Yu GL, Li Y, Parmelee D, Xing L, Coleman TA, Gentz S, Thotakura R, Nguyen N, Hesselberg M, Gentz R: Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins. J Biol Chem 1997; 272:10853-10858.
84. Stenman G, Astrom AK, Roijer E, Sotiropoulou G , Zhang M, Sager R : Assignment of a novel cysteine proteinase inhibitor (CST6) to 11q13 by fluorescence in situ hybridization. Cytogenet Cell Genet 1997; 76:45-46.
85. Schnittger S, Rao VV, Abrahamson M, Hansmann I: Cystatin C (CST3), the candidate gene for hereditary cystatin C amyloid angiopathy (HCCAA), and other members of the cystatin gene family are clustered on chromosome 20p11.2. Genomics 1993; 16:50-55.
86. Cheng T, Tjabringa GS, van Vlijmen-Willems IM, Hitomi K, van Erp PE, Schalkwijk J, Zeeuwen PL: The cystatin M/E-controlled pathway of skin barrier formation: expression of its key components in psoriasis and atopic dermatitis. Br J Dermatol 2009; 161:253-264.
87. Rivenbark AG, Livasy CA, Boyd CE, Keppler D, Coleman WB: Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions. Exp Mol Pathol 2007; 83:188-197.
88. Qiu J, Ai L, Ramachandran C, Yao B, Gopalakrishnan S, Fields CR, Delmas AL, Dyer LM, Melnick SJ, Yachnis AT, Schwartz PH, Fine HA, Brown KD, Robertson KD: Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas. Lab Invest 2008; 88:910-925.
89. Cheng T, Hitomi K, van Vlijmen-Willems IM, de Jongh GJ, Yamamoto K, Nishi K, Watts C, Reinheckel T, Schalkwijk J, Zeeuwen PL: Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for therole of cystatin M/E in epidermal cornification. J Biol Chem 2006; 281:15893-15899.
90. Sundberg JP, Boggess D, Hogan ME, Sundberg BA, Rourk MH, Harris B, Johnson K, Dunstan RW, Davisson MT: Harlequin ichthyosis (ichq): a juvenile lethal mouse mutation with ichthyosiform dermatitis. Am J Pathol 1997; 151:293-310.
91. Zeeuwen PL, van Vlijmen-Willems I M, Hendriks W , Merkx G F, Schalkwijk J: A null mutation in the cystatin M/E gene of ichq mice causes juvenile lethality and defects in epidermal cornification. Hum Mol Genet 2002; 11:2867-2875.
92. Segre JA: Epidermal barrier formation and recovery in skin disorders. J Clin Invest 2006; 116:1150-1158.
93. Zeeuwen PL, Cheng T, Schalkwijk J: The biology of cystatin M/E and its cognate target proteases. J Invest Dermatol 2009; 129:1327-1338.
94. Wille A, Gerber A, Heimburg A, Reisenauer A, Peters C, Saftig P, Reinheckel T, Welte T, Buhling F: Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells. Biol Chem 2004; 385:665-670.
95. Laurent-Matha V, Derocq D, Prebois C, Katunuma N, Liaudet-Coopman E: Processing of human cathepsin D is independent of its catalytic function and auto-activation: involvement of cathepsins L and B. J Biochem 2006; 139:363-371.
96. Higuchi K , Kawashima M ,Takagi Y ,Kondo H ,Yada Y ,Ichikawa Y ,Imokawa G: Sphingosylphosphorylcholine is an activator of transglutaminase activity in human keratinocytes. J Lipid Res 2001; 42:1562-1570.
97. Egberts F, Heinrich M, Jensen JM, Winoto-Morbach S, Pfeiffer S, Wickel M, Schunck M, Steude J, Saftig P, Proksch E, Schutze S: Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation. J Cell Sci 2004; 117:2295-2307.
98. Horikoshi T , Igarashi S ,U chiwa H ,Brysk H ,Brysk M M: R ole o f endogenous cathepsin D-like and chymotrypsin-like proteolysis in human epidermal desquamation. Br J Dermatol 1999; 141:453-459.
99. Juriaanse AC, Booij M: Isolation and characteristation of the main neutral protein from human submandibular saliva. Arch Oral Biol 1979; 24:825-828.
100. Juriaanse AC, Booij M: Isolation and partial characterisation of three acidic proteins from human submandibular saliva. Arch Oral Biol 1979; 24:621-625.
101. Minakata K, Asano M: New protein inhibitors of cysteine proteinases in human saliva and salivary glands. Hoppe Seylers Z Physiol Chem 1984; 365:399-403.
102. Obenauf SD, Fisher RH, Cowman RA, Fitzgerald RJ: Immunological relationship between anionic antimicrobial proteins from caries-free individuals and known salivary antimicrobial factors. Infect Immun 1984; 46:797-801.
103. Freije JP, Abrahamson M, Olafsson I, Velasco G, Grubb A, Lopez-Otin C: Structure and expression of the gene encoding cystatin D, a novel human cysteine proteinase inhibitor. J Biol Chem 1991; 266:20538-20543
104. Dickinson DP: Salivary (SD-type) cystatins: over one billion years in the making--but to what purpose?. Crit Rev Oral Biol Med 2002; 13:485-508.
105. Potempa J , Dubin A , Korzus G , Travis J : D egradation o f e lastin b y a cysteine proteinase from Staphylococcus aureus. J B iol C hem 1988; 263:2664-2667.
106. Hiltke TR, Lee TC, Bobek LA: Structure/function analysis of human cystatin SN and comparison of the cysteine proteinase inhibitory profiles of human cystatins C and SN. J Dent Res 1999; 78:1401-1409.
107. Abe N, Kadowaki T, Okamoto K, Nakayama K, Ohishi M, Yamamoto K: Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease. J Biochem 1998; 123:305-312.
108. Baron A, DeCarlo A, Featherstone J: Functional aspects of the human salivary cystatins in the oral environment. Oral Dis 1999; 5:234-240.
109. Chagas JR, Authie E, Serveau C, Lalmanach G, Juliano L, Gauthier F: A comparison of the enzymatic properties of the major cysteine proteinases from Trypanosoma congolense and Trypanosoma cruzi. Mol Biochem Parasitol 1997; 88:85-94.
110. Stoka V, Nycander M, Lenarcic B, Labriola C, Cazzulo JJ, Bjork I, Turk V: Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite, Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily. FEBS Lett 1995; 370:101-104.
111. Kopitar-Jerala N: Cystatins in the cells of the immune system-a current view. NY, USA: Nova Science Publishers, 2006: 127-140.
112. 112. Collins AR, Grubb A: Cystatin D, a natural salivary cysteine protease inhibitor, inhibits coronavirus replication at its physiologic concentration. Oral Microbiol Immunol 1998; 13:59-61.
113. Ruzindana-Umunyana A, Weber JM: Interactions of human lacrimal and salivary cystatins with adenovirus endopeptidase. Antiviral Res 2001; 51:203-214.
114. Gu M, Haraszthy GG, Collins AR, Bergey EJ: Identification of salivary proteins inhibiting herpes simplex virus 1 replication. Oral Microbiol Immunol 1995; 10:54-59.
115. Eriksson A, Tohonen V, Wedell A, Nordqvist K: Isolation of the human testatin gene and analysis in patients with abnormal gonadal development. Mol Hum Reprod 2002; 8:8-15.
116. Shoemaker K, Holloway JL, Whitmore TE, Maurer M, Feldhaus AL: Molecular cloning, chromosome mapping and characterization of a testis-specific cystatin-like cDNA, cystatin T. Gene 2000; 245:103-108.
117. Cornwall GA, Orgebin-Crist MC, Hann SR: The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis. Mol Endocrinol 1992; 6:1653-1664.
118. Olafsson I, Grubb A: Hereditary cystatin C amyloid angiopathy. Amyloid 2000, 7:70-79.
119. Bollengier F: Cystatin C, alias post-gamma-globulin: a marker for multiple sclerosis?. J Clin Chem Clin Biochem 1987; 25:589-593.
120. Levy E, Sastre M, Kumar A, Gallo G, Piccardo P, Ghetti B, Tagliavini F: Codeposition of cystatin C with amyloid-beta protein in the brain of Alzheimer disease patients. J Neuropathol Exp Neurol 2001; 60:94-104.
121. Sastre M , Calero M, Pawlik M, Mathews PM, Kumar A, Danilov V, Schmidt SD, Nixon RA, Frangione B, Levy E: Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation. Neurobiol Aging 2004; 25:1033-1043.
122. Mi W, Pawlik M, Sastre M, Jung SS, Radvinsky DS, Klein AM, Sommer J, Schmidt SD, Nixon RA, Mathews PM, Levy E: Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models. Nat Genet 2007; 39:1440-1442.
123. Nagai A, Ryu JK, Terashima M, Tanigawa Y, Wakabayashi K, McLarnon JG, Kobayashi S , Masuda J , Kim SU: Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with cathepsin B. Brain Res 2005; 1066:120-128.
124. Sun B, Zhou Y, Halabisky B, Lo I, Cho SH, Mueller-Steiner S, Devidze N, Wang X, Grubb A, Gan L: Cystatin C-cathepsin B axis regulates amyloid beta levels and associated neuronal deficits in an animal model of Alzheimer's disease. Neuron 2008; 60:247-257.
125. Palm DE, Knuckey NW, Primiano MJ, Spangenberger AG, Johanson CE: Cystatin C, a protease inhibitor, in degenerating rat hippocampal neurons following transient forebrain ischemia. Brain Res 1995; 691:1-8.
126. Ishimaru H, Ishikawa K, Ohe Y, Takahashi A, Maruyama Y: Cystatin C and apolipoprotein E immunoreactivities in CA1 neurons in ischemic gerbil hippocampus. Brain Res 1996; 709:155-162.
127. Lukasiuk K, Pirttila TJ, Pitkanen A: Upregulation of cystatin C expression in the rat hippocampus during epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Epilepsia 2002; 43 Suppl 5:137-145.
128. Inker LA, Okparavero A: Cystatin C as a marker of glomerular filtration rate: prospects and limitations. Curr Opin Nephrol Hypertens 2011; 20:631-639.
129. Dworkin LD: Serum cystatin C as a marker of glomerular filtration rate. Curr Opin Nephrol Hypertens 2001; 10:551-553.
130. Laterza OF, Price CP, Scott MG: Cystatin C : an improved e stimator of glomerular filtration rate?. Clin Chem 2002; 48:699-707.
131. Kos J , Š tabuc B , C imerman N , B runner N : S erum c ystatin C , a new marker of glomerular filtration rate, is increased during malignant progression. Clin Chem 1998; 44:2556-2557.
132. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJ, O'Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WH: Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38:441-446.
133. Hollox EJ, Huffmeier U, Zeeuwen PL, Palla R, Lascorz J, Rodijk-Olthuis D, van de Kerkhof PC, Traupe H, de Jongh G, den Heijer M, Reis A, Armour JA, Schalkwijk J: Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008; 40:23-25.
134. de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramis G, Ballana E, Martin-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I,Eichler EE, Lazaro C, Pujol RM,Armengol L ,Abecasis G , Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X:Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 2009; 41:211-215.
135. Ma J, Tanaka KF, Shimizu T, Bernard CC, Kakita A, Takahashi H, Pfeiffer SE, Ikenaka K: Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination. J Neurosci Res 2011; 89:639-649.
136. Pellagatti A, Vetrie D, Langford CF, Gama S, Eagleton H, Wainscoat JS, Boultwood J: Gene expression profiling in polycythemia vera using cDNA microarray technology. Cancer Res 2003, 63:3940-3944.
137. Steinau M, Unger ER, Vernon SD, Jones JF, Rajeevan MS: Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome. J Mol Med (Berl) 2004; 82:750-755.
138. Werle B, Sauckel K, Nathanson CM, Bjarnadottir M, Spiess E, Ebert W, Abrahamson M: Cystatins C , E/M a nd F in human pleural fluids of patients with neoplastic and inflammatory lung disorders. Biol Chem 2003; 384:281-28.
139. Henskens YM, van der Velden U, Veerman EC, Nieuw Amerongen AV: Protein, albumin and cystatin concentrations in saliva of healthy subjects and of patients with gingivitis or periodontitis. J Periodontal Res 1993; 28:43-48.
140. Strojnik T, Zajc I, Bervar A, Zidanik B, Golouh R, Kos J, Dolenc V, Lah T: Cathepsin B and its inhibitor stefin A in brain tumors. Pflugers Arch 2000; 439:R122-123.
141. Kos J, Werle B, Lah T, Brunner N: Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. Int J Biol Markers 2000; 15:84-89.
142. Pham CT, Ley TJ: Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci U S A 1999; 96:8627-8632.
143. Werle B, Schanzenbacher U, Lah TT, Ebert E, Jülke B, Ebert W, Fiehn W, Kayser K, Spiess E , Abrahamson M, Kos J : Cystatins in n on-small cell lung cancer: tissue levels, localization and relation to prognosis. Oncol Rep 2006; 16:647-655.
144. Cox JL, Sexton PS, Green TJ, Darmani NA: Inhibition of B16 melanoma metastasis by overexpression of the cysteine proteinase inhibitor cystatin C. Melanoma Res 1999; 9:369-374.
145. Zhang J, Shridhar R, Dai Q, Song J, Barlow SC, Yin L, Sloane BF, Miller FR, Meschonat C, Li BD, Abreo F, Keppler D: Cystatin M: a novel candidate tumor suppressor gene for breast cancer. Cancer Res 2004; 64:6957-6964.
146. Utsunomiya T, Hara Y, Kataoka A, Morita M, Arakawa H, Mori M, Nishimura S: Cystatin-like metastasis-associated protein mRNA expression in human colorectal cancer is associated with both liver metastasis and patient survival. Clin Cancer Res 2002; 8:2591-2594.
147. Hartmann S, Schonemeyer A, Sonnenburg B, Vray B, Lucius R: Cystatins of filarial nematodes up-regulate the nitric oxide production of interferon-gamma-activated murine macrophages. Parasite Immunol 2002; 24:253-262.
148. Das L, Datta N, Bandyopadhyay S, Das PK: Successful therapy of lethal murine visceral leishmaniasis with cystatin involves up-regulation of nitric oxide and a favorable T cell response. J Immunol 2001; 166:4020-4028.
149. Verdot L, Lalmanach G, Vercruysse V, Hartmann S, Lucius R, Hoebeke J, Gauthier F, Vray B: Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages. J Biol Chem 1996; 271:28077-28081.
150. Sokol JP, Schiemann WP: Cystatin C antagonizes transforming growth factor beta signaling in normal and cancer cells. Mol Cancer Res 2004; 2:183-195.
151. Blobe GC, Schiemann WP, Lodish HF: Role of transforming growth factor beta in human disease. N Engl J Med 2000; 342:1350-1358.
152. Massague J, Blain SW, Lo RS: TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 2000; 103:295-309.
153. Swallow CJ, Partridge EA, Macmillan JC, Tajirian T, DiGuglielmo GM, Hay K, Szweras M, Jahnen-Dechent W, Wrana JL, Redston M, Gallinger S, Dennis JW: alpha2HS-glycoprotein, an antagonist of transforming growth factor beta in vivo, inhibits intestinal tumor progression. Cancer Res 2004; 64:6402-6409.
154. Ai L, Kim WJ, Kim TY, Fields CR, Massoll N A, Robertson KD, Brown KD: Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Cancer Res 2006; 66:7899-7909.
155. Shridhar R, Zhang J, Song J, Booth BA, Kevil CG, Sotiropoulou G, Sloane BF, Keppler D: Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells. Oncogene 2004; 23:2206-2215
156. Song J, Jie C, Polk P, Shridhar R, Clair T, Zhang J, Yin L, Keppler D: The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells: down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin. Biochem Biophys Res Commun 2006; 340:175-182.
157. Rivenbark AG, Jones WD, Coleman WB: DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Lab Invest 2006; 86:1233-1242.
158. Schagdarsurengin U, Pfeifer GP, Dammann R: Frequent epigenetic inactivation of cystatin M in breast carcinoma. Oncogene 2007; 26:3089-3094.
159. Kos J, Krašovec M, Cimerman N, Nielsen HJ, Christensen IJ, Brünner N: Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. Clin Cancer Res 2000; 6:505-511.