A new role for Zn(II) aminopeptidases: Antigenic peptide generation and destruction

Current Pharmaceutical Design

Volumn 15, Issue 31, 2009, Pages 3656-3670

  Evnouchidou, Irini ^a   Papakyriakou, Athanasios ^a   Stratikos, Efstratios ^a  

^a INSTITUTE OF NANOSCIENCE AND NANOTECHNOLOGY   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

1,10 PHENANTHROLINE; ACTINONIN; AMASTATIN; AMINOPEPTIDASE; AMINOPEPTIDASE INHIBITOR; ARPHAMENINE A; ARPHAMENINE B; BESTATIN; BLEOMYCIN HYDROLASE; CAPTOPRIL; CYTOSOL AMINOPEPTIDASE; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 2; ENZYME INHIBITOR; EPITOPE; LEUCINETHIOL; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PROTEASOME; PUROMYCIN; PUROMYCIN AMINOPEPTIDASE; SMALL INTERFERING RNA; TRIPEPTIDYL PEPTIDASE II; UNCLASSIFIED DRUG; ZINC AMINOPEPTIDASE;

ADAPTIVE IMMUNITY; ALLELE; AMINO TERMINAL SEQUENCE; ANKYLOSING SPONDYLITIS; ANTIGEN EXPRESSION; ANTIGEN PRESENTATION; AUTOIMMUNITY; CARBOXY TERMINAL SEQUENCE; CD8+ T LYMPHOCYTE; CELLULAR DISTRIBUTION; CYTOTOXIC T LYMPHOCYTE; DOWN REGULATION; DRUG ACTIVITY; ENZYME ACTIVITY; ENZYME SPECIFICITY; ENZYME STRUCTURE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HUMAN; HYDROLYSIS; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOPATHOGENESIS; INNATE IMMUNITY; KNOCKOUT MOUSE; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; QUALITATIVE ANALYSIS; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; UPREGULATION; UTERINE CERVIX CANCER; VIRUS MENINGITIS;

AMINOPEPTIDASES; ANIMALS; ANTIGEN PRESENTATION; ENDOPLASMIC RETICULUM; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; PROTEIN PRECURSORS; T-LYMPHOCYTES, CYTOTOXIC; ZINC;

EID: 70449562278     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209789271816     Document Type: Review

References (131)

1. van der Merwe PA, Davis SJ. Molecular interactions mediating T cell antigen recognition. Annu Rev Immunol 2003; 21: 659-684 (Pubitemid 37174544)
2. Marrack P, Scott-Browne JP, Dai S, Gapin L, Kappler JW. Evolutionarily conserved amino acids that control TCR-MHC interaction. Annu Rev Immunol 2008; 26: 171-203. (Pubitemid 351600374)
3. Bjorkman, PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 1987; 329: 506-512 (Pubitemid 17131093)
4. Rock KL, Goldberg AL. Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 1999; 17: 739-779 (Pubitemid 29241139)
5. Shastri N, Schwab S, Serwold T. Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. Annu Rev Immunol 2002; 20: 463-493 (Pubitemid 34293432)
6. Natarajan K, Li H, Mariuzza RA, Margulies DH. MHC class I molecules, structure and function. Rev Immunogenet 1999; 1: 32-46.
7. Jardetzky, T. Not just another Fab: the crystal structure of a TcRMHC-peptide complex. Structure 1997; 5: 159-163 (Pubitemid 27158723)
8. Krummel MF, Davis MM. Dynamics of the immunological synapse: finding, establishing and solidifying a connection. Curr Opin Immunol 2002; 14: 66-74.
9. Jacobelli J, Andres PG, Boisvert J, Krummel MF. New views of the immunological synapse: variations in assembly and function. Curr Opin Immunol 2004; 16: 345-352 (Pubitemid 38595373)
10. Friedl P, den Boer AT, Gunzer M. Tuning immune responses: diversity and adaptation of the immunological synapse. Nat Rev Immunol 2005; 5: 532-545 (Pubitemid 40961331)
11. Davis DM, Dustin ML. What is the importance of the immunological synapse? Trends Immunol 2004; 25: 323-327
12. Davis DM. Assembly of the immunological synapse for T cells and NK cells. Trends Immunol 2002; 23: 356-363
13. Dennert G. Molecular mechanism of target lysis by cytotoxic T cells. Int Rev Immunol 1997; 14: 133-152 (Pubitemid 27185945)
14. Atkinson EA, Bleackley RC. Mechanisms of lysis by cytotoxic T cells. Crit Rev Immunol 1995; 15: 359-384
15. Andersen MH, Schrama D, Thor Straten P, Becker JC. Cytotoxic T cells. J Invest Dermatol 2006; 126: 32-41.
16. Groothuis TA, Griekspoor AC, Neijssen JJ, Herberts CA, Neefjes JJ. MHC class I alleles and their exploration of the antigen-processing machinery. Immunol Rev 2005; 207: 60-76. (Pubitemid 41415008)
17. Biddison WE, Martin R. Peptide binding motifs for MHC class I and II molecules. Curr Protoc Immunol 2001; Appendix 1: Appendix 1I.
18. Buus S. Description and prediction of peptide-MHC binding: the 'human MHC project'. Curr Opin Immunol 1999; 11: 209-213
19. Serwold T, Gaw S, Shastri N. ER aminopeptidases generate a unique pool of peptides for MHC class I molecules. Nat Immunol 2001; 2: 644-651 (Pubitemid 32677633)
20. Kanaseki T, Blanchard N, Hammer GE, Gonzalez F, Shastri N. ERAAP synergizes with MHC class I molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum. Immunity 2006; 25: 795-806. (Pubitemid 46107289)
21. Engelhard VH. Structure of peptides associated with MHC class I molecules. Curr Opin Immunol 1994; 6: 13-23. (Pubitemid 124005676)
22. Voges D, Zwickl P, Baumeister W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 1999; 68: 1015-1068 (Pubitemid 29449214)
23. Michalek MT, Grant EP, Gramm C, Goldberg AL, Rock KL. A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation. Nature 1993; 363: 552-554 (Pubitemid 23186643)
24. Yewdell J. To DRiP or not to DRiP: generating peptide ligands for MHC class I molecules from biosynthesized proteins. Mol Immunol 2002; 39: 139-146 (Pubitemid 35013507)
25. Norbury CC, Tewalt EF. Upstream toward the "DRiP"-ing source of the MHC class I pathway. Immunity 2006; 24: 503-506
26. Cascio P, Hilton C, Kisselev AF, Rock KL, Goldberg AL. 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide. EMBO J 2001; 20: 2357-2366 (Pubitemid 32452853)
27. Kisselev AF, Akopian T, Woo KM, Goldberg AL. The sizes of peptides generated from protein by mammalian 26 and 20S proteasomes. Implications for understanding the degradative mechanism and antigen presentation. J Biol Chem 1999; 274: 3363-3371 (Pubitemid 29077173)
28. Momburg F, Hammerling GJ. Generation and TAP-mediated transport of peptides for major histocompatibility complex class I molecules. Adv Immunol 1998; 68: 191-256. (Pubitemid 28188794)
29. Momburg F, Neefjes JJ, Hammerling GJ. Peptide selection by MHC-encoded TAP transporters. Curr Opin Immunol 1994; 6: 32-37 (Pubitemid 24050702)
30. Tanaka K. Role of proteasomes modified by interferon-gamma in antigen processing. J Leukoc Biol 1994; 56: 571-575 (Pubitemid 24348814)
31. Rivett AJ, Hearn AR. Proteasome function in antigen presentation: immunoproteasome complexes, Peptide production, and interactions with viral proteins. Curr Protein Pept Sci 2004; 5: 153-161
32. Van den Eynde BJ, Morel S. Differential processing of class-I-restricted epitopes by the standard proteasome and the immunoproteasome. Curr Opin Immunol 2001; 13: 147-153 (Pubitemid 32176032)
33. Fruci D, Niedermann G, Butler RH, van Endert PM. Efficient MHC class I-independent amino-terminal trimming of epitope precursor peptides in the endoplasmic reticulum. Immunity 2001; 15: 467-476 (Pubitemid 32907393)
34. York IA, Goldberg AL, Mo XY, Rock KL. Proteolysis and class I major histocompatibility complex antigen presentation. Immunol Rev 1999; 172: 49-66. (Pubitemid 30000468)
35. Rock KL, York IA, Saric T, Goldberg AL. Protein degradation and the generation of MHC class I-presented peptides. Adv Immunol 2002; 80: 1-70. (Pubitemid 34625620)
36. Shastri N, Schwab S, Serwold T. Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. Annu Rev Immunol 2002; 20: 463-493 (Pubitemid 34293432)
37. Paulsson KM, Jevon M, Wang JW, Li S, Wang P. The double lysine motif of tapasin is a retrieval signal for retention of unstable MHC class I molecules in the endoplasmic reticulum. J Immunol 2006; 176: 7482-7488 (Pubitemid 43849051)
38. Schoenhals GJ, Krishna RM, Grandea AG, 3rd,Spies T, Peterson PA, Yang Y, et al. Retention of empty MHC class I molecules by tapasin is essential to reconstitute antigen presentation in invertebrate cells. EMBO J 1999; 18: 743-753
39. Fahnestock ML, Tamir I, Narhi L, Bjorkman PJ. Thermal stability comparison of purified empty and peptide-filled forms of a class I MHC molecule. Science 1992; 258: 1658-1662 (Pubitemid 23012440)
40. Saric T, Chang SC, Hattori A, York IA, Markant S, Rock KL, et al. An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Nat Immunol 2002; 3: 1169-1176 (Pubitemid 35476828)
41. Serwold T, Gonzalez F, Kim J, Jacob R, Shastri N. ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 2002; 419: 480-483 (Pubitemid 34293432)
42. York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol 2002; 3: 1177-1184 (Pubitemid 35469702)
43. Hammer GE, Gonzalez F, James E, Nolla H, Shastri N. In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Nat Immunol 2007; 8: 101-108
44. Hattori A, Matsumoto H, Mizutani S, Tsujimoto M. Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase. J Biochem (Tokyo) 1999; 125: 931-938 (Pubitemid 29253563)
45. Schomburg L, Kollmus H, Friedrichsen S, Bauer K. Molecular characterization of a puromycin-insensitive leucyl-specific aminopeptidase, PILS-AP. Eur J Biochem 2000; 267: 3198-3207 (Pubitemid 30341146)
46. Cui XL, Hawari F, Alsaaty S, Lawrence M, Combs CA, Geng WD, et al. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest 2002; 110: 515-526 (Pubitemid 34919706)
47. Yamamoto N, Nakayama J, Yamakawa-Kobayashi K, Hamaguchi H, Miyazaki R, Arinami T. Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension. Hum Mutat 2002; 19: 251-257 (Pubitemid 34195186)
48. Lew RA, Mustafa T, Ye SY, McDowall SG, Chai SY, Albiston AL. Angiotensin AT(4) ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP). J Neurochem 2003; 86: 344-350
49. Hallberg P, Lind L, Michaelsson K, Kurland L, Kahan T, Malmqvist K, et al. Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy. BMC Cardiovasc Disord 2003; 3: 11. (Pubitemid 38824811)
50. Akada T, Yamazaki T, Miyashita H, Niizeki O, Abe M, Sato A, et al. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial Integrins. J Cell Physiol 2002; 193: 253-262 (Pubitemid 46683039)
51. Watanabe Y, Shibata K, Kikkawa F, Kajiyama H, Ino K, Hattori A, et al. Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system. Clin Cancer Res 2003; 9: 6497-6503 (Pubitemid 38031839)
52. Cui XL, Rouhani FN, Hawari F, Levine SJ. An aminopeptidase, ARTS-1, is required for interleukin-6 receptor shedding. J Biol Chem 2003; 278: 28677-28685 (Pubitemid 36935774)
53. Cui X, Rouhani FN, Hawari F, Levine SJ. Shedding of the type II IL-1 decoy receptor requires a multifunctional aminopeptidase, aminopeptidase regulator of TNF receptor type 1 shedding. J Immunol 2003; 171: 6814-6819 (Pubitemid 37532116)
54. Tanioka T, Hattori A, Masuda S, Nomura Y, Nakayama H, Mizutani S, et al. Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. J Biol Chem 2003; 278: 32275-32283 (Pubitemid 37048421)
55. Yamamoto N, Nakayama J, Yamakawa-Kobayashi K, Hamaguchi H, Miyazaki R, Arinami T. Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension. Hum Mutat 2002; 19: 251-257 (Pubitemid 34195186)
56. Hattori A, Kitatani K, Matsumoto H, Miyazawa S, Rogi T, Tsuruoka N, et al. Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells. J Biochem (Tokyo) 2000; 128: 755-762
57. Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, et al. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol 2005; 6: 689-697 (Pubitemid 41716742)
58. Rawlings ND, Barrett AJ. Evolutionary families of metallopeptidases. Methods Enzymol 1995; 248: 183-228.
59. Rawlings ND, Morton FR, Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res 2006; 34: D270-2.
60. Albiston AL, Ye S, Chai SY. Membrane bound members of the M1 family: more than aminopeptidases. Protein Pept Lett 2004; 11: 491-500. (Pubitemid 39197500)
61. Tsujimoto M, Hattori A. The oxytocinase subfamily of M1 aminopeptidases. Biochim Biophys Acta 2005; 1751: 9-18.
62. Hooper NM. Families of zinc metalloproteases. FEBS Lett 1994; 354: 1-6.
63. Iturrioz X, Rozenfeld R, Michaud A, Corvol P, Llorens-Cortes C. Study of asparagine 353 in aminopeptidase A: characterization of a novel motif (GXMEN) implicated in exopeptidase specificity of monozinc aminopeptidases. Biochemistry 2001; 40: 14440-14448 (Pubitemid 33111726)
64. Matthews BW. Structural basis of the action of thermolysin and related zinc peptidases. Acc Chem Res 1988; 21: 333-340
65. Goto Y, Tanji H, Hattori A, Tsujimoto M. Glutamine-181 is crucial in the enzymatic activity and substrate specificity of human endoplasmic-reticulum aminopeptidase-1. Biochem J 2008; 416: 109-116
66. Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schaffer AA, et al. Protein database searches using compositionally adjusted substitution matrices. Febs Journal 2005; 272: 5101-5109 (Pubitemid 41503143)
67. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res 2000; 28: 235-242
68. Tsujimoto M, Hattori A. The oxytocinase subfamily of M1 aminopeptidases. Biochim Biophys Acta-Proteins Proteomics 2005; 1751: 9-18.
69. Baker D, Sali A. Protein structure prediction and structural genomics. Science 2001; 294: 93-96 (Pubitemid 32952955)
70. Kyrieleis OJ, Goettig P, Kiefersauer R, Huber R, Brandstetter H. Crystal structures of the tricorn interacting factor F3 from Thermoplasma acidophilum, a zinc aminopeptidase in three different conformations. J Mol Biol 2005; 349: 787-800. (Pubitemid 40731533)
71. Evnouchidou I, Momburg F, Papakyriakou A, Chron A, Leondiadis L, Chang SC, et al. The internal sequence of the peptide-substrate intermediate determines its N-terminus trimming by ERAP1. PLoS ONE 2008.
72. Yan J, Parekh VV, Mendez-Fernandez Y, Olivares-Villagomez D, Dragovic S, Hill T, et al. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J Exp Med 2006; 203: 647-659
73. Firat E, Saveanu L, Aichele P, Staeheli P, Huai J, Gaedicke S, et al. The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. J Immunol 2007; 178: 2241-2248 (Pubitemid 46233422)
74. Hammer GE, Gonzalez F, Champsaur M, Cado D, Shastri N. The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules. Nat Immunol 2006; 7: 103-112 (Pubitemid 41823874)
75. York IA, Brehm MA, Zendzian S, Towne CF, Rock KL. Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance. Proc Natl Acad Sci USA 2006; 103: 9202-9207
76. Blanchard N, Gonzalez F, Schaeffer M, Joncker NT, Cheng T, Shastri AJ, et al. Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum. Nat Immunol 2008; 9: 937-944
77. Sadegh-Nasseri S, Chen M, Narayan K, Bouvier M. The convergent roles of tapasin and HLA-DM in antigen presentation. Trends Immunol 2008; 29: 141-147
78. Beninga J, Rock KL, Goldberg AL. Interferon-gamma can stimulate post-proteasomal trimming of the N terminus of an antigenic peptide by inducing leucine aminopeptidase. J Biol Chem 1998; 273: 18734-18742 (Pubitemid 28366257)
79. Stoltze L, Schirle M, Schwarz G, Schroter C, Thompson MW, Hersh LB, et al. Two new proteases in the MHC class I processing pathway. Nat Immunol 2000; 1: 413-418
80. Towne CF, York IA, Neijssen J, Karow ML, Murphy AJ, Valenzuela DM, et al. Leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for MHC class I antigen presentation. J Immunol 2005; 175: 6605-6614 (Pubitemid 41598903)
81. Levy F, Burri L, Morel S, Peitrequin AL, Levy N, Bachi A, et al. The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases. J Immunol 2002; 169: 4161-4171 (Pubitemid 35178186)
82. Reits E, Neijssen J, Herberts C, Benckhuijsen W, Janssen L, Drijfhout JW, et al. A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation. Immunity 2004; 20: 495-506. (Pubitemid 38482126)
83. Kloetzel PM. Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat Immunol 2004; 5: 661-669
84. Kim SI, Pabon A, Swanson TA, Glucksman MJ. Regulation of cell-surface major histocompatibility complex class I expression by the endopeptidase EC3.4.24.15 (thimet oligopeptidase). Biochem J 2003; 375: 111-120 (Pubitemid 37255386)
85. York IA, Bhutani N, Zendzian S, Goldberg AL, Rock KL. Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentation. J Immunol 2006; 177: 1434-1443 (Pubitemid 44092476)
86. Chang SC, Momburg F, Bhutani N, Goldberg AL. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism. Proc Natl Acad Sci USA 2005; 102: 17107-17112
87. Kanaseki T, Shastri N. Endoplasmic reticulum aminopeptidase associated with antigen processing regulates quality of processed peptides presented by MHC class I molecules. J Immunol 2008; 181: 6275-6282
88. Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007; 369: 1379-1390
89. Thomas DC, Clayton DG. Betting odds and genetic associations. J Natl Cancer Inst 2004; 96: 421-423
90. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 2007; 39: 1329-1337 (Pubitemid 350041542)
91. Maksymowych WP, Inman RD, Gladman DD, Reeve JP, Pope A, Rahman P. Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in ankylosing spondylitis. Arthritis Rheum 2009; 60: 1317-1323
92. Tsui FW, Haroon N, Reveille JD, Rahman P, Chiu B, Tsui HW, et al. Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis. Ann Rheum Dis 2009 [Epub ahead of print].
93. Fung E, Smyth DJ, Howson JM, Cooper JD, Walker NM, Stevens H, et al. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes Immun 2009; 10(2): 188-191
94. Castellsague X, Diaz M, de Sanjose S, Munoz N, Herrero R, Franceschi S, et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 2006; 98: 303-315 (Pubitemid 43338210)
95. Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ. HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol 2006; 208: 152-164 (Pubitemid 43126109)
96. Seliger B, Ritz U, Ferrone S. Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. Int J Cancer 2006; 118: 129-138 (Pubitemid 41681589)
97. Lankat-Buttgereit B, Tampe R. The transporter associated with antigen processing: function and implications in human diseases. Physiol Rev 2002; 82: 187-204. (Pubitemid 34654218)
98. Gostout BS, Strome SE, Clayton AC, McGovern RM, Olsen KD, Webb MJ. Two cases of coincident carcinomas of the head and neck and the uterine cervix. Gynecol Oncol 2002; 85: 376-380
99. Fowler NL, Frazer IH. Mutations in TAP genes are common in cervical carcinomas. Gynecol Oncol 2004; 92: 914-921
100. Mehta AM, Jordanova ES, van Wezel T, Uh HW, Corver WE, Kwappenberg KM, et al. Genetic variation of antigen processing machinery components and association with cervical carcinoma. Genes Chromosomes Cancer 2007; 46: 577-586 (Pubitemid 46649572)
101. Mehta AM, Jordanova ES, Corver WE, van Wezel T, Uh HW, Kenter GG, et al. Single nucleotide polymorphisms in antigen processing machinery component ERAP1 significantly associate with clinical outcome in cervical carcinoma. Genes Chromosomes Cancer 2009; 48: 410-418
102. Goto Y, Hattori A, Ishii Y, Tsujimoto M. Reduced activity of the hypertension-associated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-1. FEBS Lett 2006; 580: 1833-1838.
103. Qu HQ, Marchand L, Frechette R, Bacot F, Lu Y, Polychronakos C. No association of type 1 diabetes with a functional polymorphism of the LRAP gene. Mol Immunol 2007; 44: 2135-2138
104. Mehta AM, Jordanova ES, Kenter GG, Ferrone S, Fleuren GJ. Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol Immunother 2008; 57: 197-206. (Pubitemid 350159921)
105. Fruci D, Giacomini P, Nicotra MR, Forloni M, Fraioli R, Saveanu L, et al. Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues. J Cell Physiol 2008; 216: 742-749
106. Wardle NJ, Bligh SW, Hudson HR. Organophosphorus compounds: intervention in mechanisms of signal transduction relevant to proliferative, immunological and circulatory disorders. Curr Med Chem 2008; 15: 2230-2257
107. Thielitz A, Ansorge S, Bank U, Tager M, Wrenger S, Gollnick H, et al. The ectopeptidases dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and their related enzymes as possible targets in the treatment of skin diseases. Front Biosci 2008; 13: 2364-2375 (Pubitemid 351589260)
108. Albiston AL, Peck GR, Yeatman HR, Fernando R, Ye S, Chai SY. Therapeutic targeting of insulin-regulated aminopeptidase: heads and tails? Pharmacol Ther 2007; 116: 417-427
109. Bauvois B, Dauzonne D. Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects. Med Res Rev 2006; 26: 88-130. (Pubitemid 43986471)
110. Banegas I, Prieto I, Vives F, Alba F, de Gasparo M, Segarra AB, et al. Brain aminopeptidases and hypertension. J Renin Angiotensin Aldosterone Syst 2006; 7: 129-134
111. Xu W, Li Q. Progress in the development of aminopeptidase N (APN/CD13) inhibitors. Curr Med Chem Anticancer Agents 2005; 5: 281-301. (Pubitemid 40645595)
112. Magy L, Vincent F, Faure S, Messerli FH, Wang JG, Achard JM, et al. The renin-angiotensin systems: evolving pharmacological perspectives for cerebroprotection. Curr Pharm Des 2005; 11: 3275-3291 (Pubitemid 41300777)
113. Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, et al. The angiotensin IV/AT4 receptor. Cell Mol Life Sci 2004; 61: 2728-2737
114. Sato Y. Aminopeptidases and angiogenesis. Endothelium 2003; 10: 287-290
115. Baxter GF, Ebrahim Z. Role of bradykinin in preconditioning and protection of the ischaemic myocardium. Br J Pharmacol 2002; 135: 843-854 (Pubitemid 34214443)
116. David-Basei C, Fournie-Zaluski MC, Rogues BP. Aminopeptidase A inhibitors. Expert Opin Therapeut Patents 2001; 11: 431-444
117. Grembecka J, Kafarski P. Leucine aminopeptidase as a target for inhibitor design. Mini Rev Med Chem 2001; 1: 133-144
118. Rawlings ND, Morton FR, Kok CY, Kong J, Barrett AJ. MEROPS: the peptidase database. Nucleic Acids Res 2008; 36: D320-5.
119. Umezawa H, Aoyagi T, Suda H, Hamada M, Takeuchi T. Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes. J Antibiot (Tokyo) 1976; 29: 97-99
120. Kim H, Lipscomb WN. X-ray crystallographic determination of the structure of bovine lens leucine aminopeptidase complexed with amastatin: formulation of a catalytic mechanism featuring a gemdiolate transition state. Biochemistry 1993; 32: 8465-8478 (Pubitemid 23270427)
121. Tieku S, Hooper NM. Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme. Biochem Pharmacol 1992; 44: 1725-1730
122. Thunnissen MM, Andersson B, Samuelsson B, Wong CH, Haeggstrom JZ. Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors. FASEB J 2002; 16: 1648-1650
123. Harbeson SL, Rich DH. Inhibition of arginine aminopeptidase by bestatin and arphamenine analogues. Evidence for a new mode of binding to aminopeptidases. Biochemistry 1988; 27: 7301-7310
124. Fujii H, Nakajima M, Aoyagi T, Tsuruo T. Inhibition of tumor cell invasion and matrix degradation by aminopeptidase inhibitors. Biol Pharm Bull 1996; 19: 6-10. (Pubitemid 26060548)
125. Aoyagi T, Yoshida S, Matsuda N, Ikeda T, Hamada M, Takeuchi T. Leuhistin, a new inhibitor of aminopeptidase M, produced by Bacillus laterosporus BMI156-14F1. I. Taxonomy, production, isolation, physico-chemical properties and biological activities. J Antibiot (Tokyo) 1991; 44: 573-578
126. Albiston AL, Morton CJ, Ng HL, Pham V, Yeatman HR, Ye S, et al. Identification and characterization of a new cognitive enhancer based on inhibition of insulin-regulated aminopeptidase. FASEB J 2008.
127. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, et al. Clustal W and clustal X version 2.0. Bioinformatics 2007; 23: 2947-2948
128. Clamp M, Cuff J, Searle SM, Barton GJ. The Jalview Java alignment editor. Bioinformatics 2004; 20: 426-427
129. Magrone T, Tafaro A, Jirillo F, Amati L, Jirillo E, Covelli V. Elicitation of immune responsiveness against antigenic challenge in age-related diseases: effects of red wine polyphenols. Curr Pharm Des 2008; 14(26): 2749-2757
130. Mizrahi M, Ilan Y. The gut mucosa as a site for induction of regulatory T-cells. Curr Pharm Des 2009; 15(11): 1191-1202
131. Wong JP, Christopher ME, Viswanathan S, Dai X, Salazar AM, Sun LQ, et al. Antiviral role of toll-like receptor-3 agonists against seasonal and avian influenza viruses. Curr Pharm Des 2009; 15(11): 1269-1274