Role of endoplasmic reticulum aminopeptidases in health and disease: From infection to cancer

International Journal of Molecular Sciences

Volumn 13, Issue 7, 2012, Pages 8338-8352

  Cifaldi, Loredana ^a   Romania, Paolo ^a   Lorenzi, Silvia ^a   Locatelli, Franco ^a,b   Fruci, Doriana ^a  

^a BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

Author keywords

Antigen processing; Autoimmunity; Cancer; Cancer immunotherapy; Endoplasmic reticulum aminopeptidases; MHC class I; Viral infection

Indexed keywords

AMINOPEPTIDASE; ANGIOTENSIN II; ENDOPLASMIC RETICULUM AMINOPEPTIDASE; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 2; HLA B27 ANTIGEN; INTERLEUKIN 1 RECEPTOR TYPE II; INTERLEUKIN 6 RECEPTOR ALPHA; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; TUMOR NECROSIS FACTOR RECEPTOR 1; UNCLASSIFIED DRUG; ERAP1 PROTEIN, HUMAN; ERAP2 PROTEIN, HUMAN;

ANGIOGENESIS; ANTIGEN PRESENTATION; AUTOIMMUNE DISEASE; BLOOD PRESSURE REGULATION; CD8+ T LYMPHOCYTE; CYTOMEGALOVIRUS INFECTION; CYTOTOXIC T LYMPHOCYTE; DISEASE PREDISPOSITION; ENDOPLASMIC RETICULUM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; IMMUNE EVASION; IMMUNOGENICITY; INFECTION; LYMPHOCYTIC CHORIOMENINGITIS; NATURAL KILLER CELL; NEOPLASM; NONHUMAN; PAPILLOMAVIRUS INFECTION; REVIEW; TOXOPLASMOSIS; UTERINE CERVIX CARCINOMA; ANIMAL; BACTERIAL INFECTION; ENZYMOLOGY; PHYSIOLOGY; PROTEIN DEGRADATION; PROTEIN PROCESSING; VIRUS INFECTION;

AMINOPEPTIDASES; ANIMALS; BACTERIAL INFECTIONS; ENDOPLASMIC RETICULUM; HUMANS; NEOPLASMS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOLYSIS; VIRUS DISEASES;

EID: 84864376114     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms13078338     Document Type: Review

References (75)

1. Hattori, A.; Matsumoto, H.; Mizutani, S.; Tsujimoto, M. Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase. J. Biochem. 1999, 125, 931-938.
2. Andres, A.M.; Dennis, M.Y.; Kretzschmar, W.W.; Cannons, J.L.; Lee-Lin, S.Q.; Hurle, B.; Schwartzberg, P.L.; Williamson, S.H.; Bustamante, C.D.; Nielsen, R.; et al. Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS Genet. 2010, 6, e1001157. Available online: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001157 (accessed on 29 June 2012).
3. Saric, T.; Chang, S.C.; Hattori, A.; York, I.A.; Markant, S.; Rock, K.L.; Tsujimoto, M.; Goldberg, A.L. An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Nat. Immunol. 2002, 3, 1169-1176.
4. Shin, E.C.; Seifert, U.; Urban, S.; Truong, K.T.; Feinstone, S.M.; Rice, C.M.; Kloetzel, P.M.; Rehermann, B. Proteasome activator and antigen-processing aminopeptidases are regulated by virus-induced type I interferon in the hepatitis C virus-infected liver. J. Interferon Cytokine Res. 2007, 27, 985-990.
5. 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.
6. Tanioka, T.; Hattori, A.; Masuda, S.; Nomura, Y.; Nakayama, H.; Mizutani, S.; Tsujimoto, M. Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. J. Biol. Chem. 2003, 278, 32275-32283.
7. Forloni, M.; Albini, S.; Limongi, M.Z.; Cifaldi, L.; Boldrini, R.; Nicotra, M.R.; Giannini, G.; Natali, P.G.; Giacomini, P.; Fruci, D. NF-kappaB, and not MYCN, regulates MHC class I and endoplasmic reticulum aminopeptidases in human neuroblastoma cells. Cancer Res. 2010, 70, 916-924.
8. York, I.A.; Chang, S.C.; Saric, T.; Keys, J.A.; Favreau, J.M.; Goldberg, A.L.; Rock, K.L.The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat. Immunol. 2002, 3, 1177-1184.
9. Saveanu, L.; Carroll, O.; Lindo, V.; Del Val, M.; Lopez, D.; Lepelletier, Y.; Greer, F.; Schomburg, L.; Fruci, D.; Niedermann, G.; et al. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat. Immunol. 2005, 6, 689-697.
10. Cui, X.; Hawari, F.; Alsaaty, S.; Lawrence, M.; Combs, C.A.; Geng, W.; Rouhani, F.N.; Miskinis, D.; Levine, S.J. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J. Clin. Invest. 2002, 110, 515-526.
11. Cui, X.; Rouhani, F.N.; Hawari, F.; Levine, S.J. 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.
12. Cui, X.; Rouhani, F.N.; Hawari, F.; Levine, S.J. An aminopeptidase, ARTS-1, is required for interleukin-6 receptor shedding. J. Biol. Chem. 2003, 278, 28677-28685.
13. Sato, Y. Role of aminopeptidase in angiogenesis. Biol. Pharm. Bull. 2004, 27, 772-776.
14. Hattori, A.; Kitatani, K.; Matsumoto, H.; Miyazawa, S.; Rogi, T.; Tsuruoka, N.; Mizutani, S.; Natori, Y.; Tsujimoto, M. Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells. J. Biochem. 2000, 128, 755-762.
15. Neefjes, J.; Jongsma, M.L.; Paul, P.; Bakke, O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol. 2011, 11, 823-836.
16. Kloetzel, P.M. Generation of major histocompatibility complex class I antigens: Functional interplay between proteasomes and TPPII. Nat. Immunol. 2004, 5, 661-669.
17. Reits, E.; Neijssen, J.; Herberts, C.; Benckhuijsen, W.; Janssen, L.; Drijfhout, J.W.; Neefjes, J. A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation. Immunity 2004, 20, 495-506.
18. Seifert, U.; Maranon, C.; Shmueli, A.; Desoutter, J.F.; Wesoloski, L.; Janek, K.; Henklein, P.; Diescher, S.; Andrieu, M.; de la Salle, H.; et al. An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope. Nat. Immunol. 2003, 4, 375-379.
19. Beninga, J.; Rock, K.L.; Goldberg, A.L. 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.
20. Paz, P.; Brouwenstijn, N.; Perry, R.; Shastri, N. Discrete proteolytic intermediates in the MHC class I antigen processing pathway and MHC I-dependent peptide trimming in the ER. Immunity 1999, 11, 241-251.
21. Stoltze, L.; Nussbaum, A.K.; Sijts, A.; Emmerich, N.P.; Kloetzel, P.M.; Schild, H. The function of the proteasome system in MHC class I antigen processing. Immunol. Today 2000, 21, 317-319.
22. Stoltze, L.; Schirle, M.; Schwarz, G.; Schroter, C.; Thompson, M.W.; Hersh, L.B.; Kalbacher, H.; Stevanovic, S.; Rammensee, H.G.; Schild, H. Two new proteases in the MHC class I processing pathway. Nat. Immunol. 2000, 1, 413-418.
23. Lauvau, G.; Kakimi, K.; Niedermann, G.; Ostankovitch, M.; Yotnda, P.; Firat, H.; Chisari, F.V.; van Endert, P.M. Human transporters associated with antigen processing (TAPs) select epitope precursor peptides for processing in the endoplasmic reticulum and presentation to T cells. J. Exp. Med. 1999, 190, 1227-1240.
24. Chang, S.C.; Momburg, F.; Bhutani, N.; Goldberg, A.L. 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.
25. 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.
26. Evnouchidou, I.; Momburg, F.; Papakyriakou, A.; Chroni, A.; Leondiadis, L.; Chang, S.C.; Goldberg, A.L.; Stratikos, E. The internal sequence of the peptide-substrate determines its N-terminus trimming by ERAP1. PLoS One 2008, 3, e3658.
27. Hammer, G.E.; 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.
28. Yan, J.; Parekh, V.V.; Mendez-Fernandez, Y.; Olivares-Villagomez, D.; Dragovic, S.; Hill, T.; Roopenian, D.C.; Joyce, S.; van Kaer, L. 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.
29. Firat, E.; Saveanu, L.; Aichele, P.; Staeheli, P.; Huai, J.; Gaedicke, S.; Nil, A.; Besin, G.; Kanzler, B.; van Endert, P.; et al. The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. J. Immunol. 2007, 178, 2241-2248.
30. York, I.A.; Brehm, M.A.; Zendzian, S.; Towne, C.F.; Rock, K.L. 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.
31. Hammer, G.E.; 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.
32. Blanchard, N.; Shastri, N. Coping with loss of perfection in the MHC class I peptide repertoire. Curr. Opin. Immunol. 2008, 20, 82-88.
33. Blanchard, N.; Kanaseki, T.; Escobar, H.; Delebecque, F.; Nagarajan, N.A.; Reyes-Vargas, E.; Crockett, D.K.; Raulet, D.H.; Delgado, J.C.; Shastri, N. Endoplasmic reticulum aminopeptidase associated with antigen processing defines the composition and structure of MHC class I peptide repertoire in normal and virus-infected cells. J. Immunol. 2010, 184, 3033-3042.
34. Nagarajan, N.A.; Gonzalez, F.; Shastri, N. Nonclassical MHC class Ib-restricted cytotoxic T cells monitor antigen processing in the endoplasmic reticulum. Nat. Immunol. 2012, 13, 579-586.
35. Miyashita, H.; Yamazaki, T.; Akada, T.; Niizeki, O.; Ogawa, M.; Nishikawa, S.; Sato, Y. A mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase is expressed in endothelial cells and plays an important role in angiogenesis. Blood 2002, 99, 3241-3249.
36. Akada, T.; Yamazaki, T.; Miyashita, H.; Niizeki, O.; Abe, M.; Sato, A.; Satomi, S.; Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial integrins. J. Cell Physiol. 2002, 193, 253-262.
37. Yamazaki, T.; Akada, T.; Niizeki, O.; Suzuki, T.; Miyashita, H.; Sato, Y. Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) binds and catalyzes PDK1, allowing VEGF-stimulated activation of S6K for endothelial cell proliferation and angiogenesis. Blood 2004, 104, 2345-52.
38. Suzuki, T.; Abe, M.; Miyashita, H.; Kobayashi, T.; Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) affects RhoA activation in endothelial cells. J. Cell Physiol. 2007, 211, 708-715.
39. Yoshida, T.; Sato, Y.; Morita, I.; Abe, M. Pigpen, a nuclear coiled body component protein, is involved in angiogenesis. Cancer Sci. 2010, 101, 1170-1176.
40. Abe, M.; Sato, Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is required for the development of vascular as well as hematopoietic system in embryoid bodies. Genes. Cells 2006, 11, 719-729.
41. Fierabracci, A.; Milillo, A.; Locatelli, F.; Fruci, D. The putative role of endoplasmic reticulum aminopeptidases in autoimmunity: Insights from genomic-wide association studies. Autoimmun. Rev. 2012, in press.
42. Taranta, A.; Gianviti, A.; Palma, A.; De Luca, V.; Mannucci, L.; Procaccino, M.A.; Ghiggeri, G.M.; Caridi, G.; Fruci, D. Genetic risk factors in typical haemolytic uraemic syndrome. Nephrol. Dial. Transplant. 2009, 24, 1851-1857.
43. 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.
44. Goto, Y.; Hattori, A.; Ishii, Y.; Mizutani, S.; Tsujimoto, M. Enzymatic properties of human aminopeptidase A. Regulation of its enzymatic activity by calcium and angiotensin IV. J. Biol. Chem. 2006, 281, 23503-23513.
45. Hallberg, P.; Lind, L.; Michaelsson, K.; Kurland, L.; Kahan, T.; Malmqvist, K.; Ohman, K.P.; Nystrom, F.; Liljedahl, U.; Syvanen, A.C.; et al. Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy. BMC Cardiovasc. Disord. 2003, 3, 11.
46. Hill, L.D.; Hilliard, D.D.; York, T.P.; Srinivas, S.; Kusanovic, J.P.; Gomez, R.; Elovitz, M.A.; Romero, R.; Strauss, J.F. Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study. BMC Med. Genet. 2011, 12, 64.
47. Johnson, M.P.; Roten, L.T.; Dyer, T.D.; East, C.E.; Forsmo, S.; Blangero, J.; Brennecke, S.P.; Austgulen, R.; Moses, E.K. The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. Hum. Genet. 2009, 126, 655-666.
48. Founds, S.A.; Conley, Y.P.; Lyons-Weiler, J.F.; Jeyabalan, A.; Hogge, W.A.; Conrad, K.P. Altered global gene expression in first trimester placentas of women destined to develop preeclampsia. Placenta 2009, 30, 15-24.
49. Blanchard, N.; Gonzalez, F.; Schaeffer, M.; Joncker, N.T.; Cheng, T.; Shastri, A.J.; Robey, E.A.; Shastri, N. Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum. Nat. Immunol. 2008, 9, 937-944.
50. Draenert, R.; Le Gall, S.; Pfafferott, K.J.; Leslie, A.J.; Chetty, P.; Brander, C.; Holmes, E.C.; Chang, S.C.; Feeney, M.E.; Addo, M.M.; et al. Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection. J. Exp. Med. 2004, 199, 905-915.
51. Tenzer, S.; Wee, E.; Burgevin, A.; Stewart-Jones, G.; Friis, L.; Lamberth, K.; Chang, C.H.; Harndahl, M.; Weimershaus, M.; Gerstoft, J. Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance. Nat. Immunol. 2009, 10, 636-646.
52. Cagliani, R.; Riva, S.; Biasin, M.; Fumagalli, M.; Pozzoli, U.; Lo Caputo, S.; Mazzotta, F.; Piacentini, L.; Bresolin, N.; Clerici, M.; et al. Genetic diversity at endoplasmic reticulum aminopeptidases is maintained by balancing selection and is associated with natural resistance to HIV-1 infection. Hum. Mol. Genet. 2010, 19, 4705-4714.
53. Mehta, A.M.; Jordanova, E.S.; Corver, W.E.; van Wezel, T.; Uh, H.W.; Kenter, G.G.; Fleuren, G.J. Single nucleotide polymorphisms in antigen processing machinery component ERAP1 significantly associate with clinical outcome in cervical carcinoma. Genes. Chromosomes Cancer 2009, 48, 410-418.
54. Kim, S.; Lee, S.; Shin, J.; Kim, Y.; Evnouchidou, I.; Kim, D.; Kim, Y.K.; Kim, Y.E.; Ahn, J.H.; Riddell, S.R.; et al. Human cytomegalovirus microRNA miR-US4-1 inhibits CD8(+) T cell responses by targeting the aminopeptidase ERAP1. Nat. Immunol. 2011, 12, 984-991.
55. Burton, P.R.; Clayton, D.G.; Cardon, L.R.; Craddock, N.; Deloukas, P.; Duncanson, A.; Kwiatkowski, D.P.; McCarthy, M.I.; Ouwehand, W.H.; Samani, N.J.; et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 2007, 39, 1329-1337.
56. Maksymowych, W.P.; Inman, R.D.; Gladman, D.D.; Reeve, J.P.; Pope, A.; Rahman, P. Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in ankylosing spondylitis. Arthritis Rheum. 2009, 60, 1317-1323.
57. Davidson, S.I.; Wu, X.; Liu, Y.; Wei, M.; Danoy, P.A.; Thomas, G.; Cai, Q.; Sun, L.; Duncan, E.; Wang, N. Association of ERAP1, but not IL23R, with ankylosing spondylitis in a Han Chinese population. Arthritis Rheum. 2009, 60, 3263-3268.
58. Choi, C.B.; Kim, T.H.; Jun, J.B.; Lee, H.S.; Shim, S.C.; Lee, B.; Pope, A.; Uddin, M.; Rahman, P.; Inman, R.D. ARTS1 polymorphisms are associated with ankylosing spondylitis in Koreans. Ann. Rheum. Dis. 2010, 69, 582-584.
59. Harvey, D.; Pointon, J.J.; Evans, D.M.; Karaderi, T.; Farrar, C.; Appleton, L.H.; Sturrock, R.D.; Stone, M.A.; Oppermann, U.; Brown, M.A.; Wordsworth, B.P.; et al. Investigating the genetic association between ERAP1 and ankylosing spondylitis. Hum. Mol. Genet. 2009, 18, 4204-4212.
60. Evans, D.M.; Spencer, C.C.; Pointon, J.J.; Su, Z.; Harvey, D.; Kochan, G.; Oppermann, U.; Dilthey, A.; Pirinen, M.; Stone, M.A. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat. Genet. 2011, 43, 761-767.
61. Pazar, B.; Safrany, E.; Gergely, P.; Szanto, S.; Szekanecz, Z.; Poor, G. Association of ARTS1 gene polymorphisms with ankylosing spondylitis in the Hungarian population: the rs27044 variant is associated with HLA-B*2705 subtype in Hungarian patients with ankylosing spondylitis. J. Rheumatol. 2010, 37, 379-384.
62. Evnouchidou, I.; Kamal, R.P.; Seregin, S.S.; Goto, Y.; Tsujimoto, M.; Hattori, A.; Voulgari, P.V.; Drosos, A.A.; Amalfitano, A.; York, I.A.; et al. Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme. J. Immunol. 2011, 186, 1909-1913.
63. Fung, E.Y.; Smyth, D.J.; Howson, J.M.; Cooper, J.D.; Walker, N.M.; Stevens, H.; Wicker, L.S.; Todd, J.A. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes. Immun. 2009, 10, 188-191.
64. Guerini, F.R.; Cagliani, R.; Forni, D.; Agliardi, C.; Caputo, D.; Cassinotti, A.; Galimberti, D.; Fenoglio, C.; Biasin, M.; Asselta, R.; et al. A functional variant in ERAP1 predisposes to multiple sclerosis. PLoS One 2012, 7, e29931.
65. Strange, A.; Capon, F.; Spencer, C.C.; Knight, J.; Weale, M.E.; Allen, M.H.; Barton, A.; Band, G.; Bellenguez, C.; Bergboer, J.G.; et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat. Genet. 2010, 42, 985-990.
66. Sun, L.D.; Cheng, H.; Wang, Z.X.; Zhang, A.P.; Wang, P.G.; Xu, J.H.; Zhu, Q.X.; Zhou, H.S.; Ellinghaus, E.; Zhang, F.R.; et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat. Genet. 2010, 42, 1005-1009.
67. Franke, A.; McGovern, D.P.; Barrett, J.C.; Wang, K.; Radford-Smith, G.L.; Ahmad, T.; Lees, C.W.; Balschun, T.; Lee, J.; Roberts, R.; et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 2010, 42, 1118-1125.
68. Fruci, D.; Ferracuti, S.; Limongi, M.Z.; Cunsolo, V.; Giorda, E.; Fraioli, R.; Sibilio, L.; Carroll, O.; Hattori, A.; van Endert, P.M.; et al. Expression of endoplasmic reticulum aminopeptidases in EBV-B cell lines from healthy donors and in leukemia/lymphoma, carcinoma, and melanoma cell lines. J. Immunol. 2006, 176, 4869-4879.
69. Fruci, D.; Giacomini, P.; Nicotra, M.R.; Forloni, M.; Fraioli, R.; Saveanu, L.; van Endert, P.; Natali, P.G. Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues. J. Cell Physiol. 2008, 216, 742-749.
70. Kamphausen, E.; Kellert, C.; Abbas, T.; Akkad, N.; Tenzer, S.; Pawelec, G.; Schild, H.; van Endert, P.; Seliger, B. Distinct molecular mechanisms leading to deficient expression of ER-resident aminopeptidases in melanoma. Cancer Immunol. Immunother. 2010, 59, 1273-1284.
71. Kazeto, H.; Nomura, S.; Ito, N.; Ito, T.; Watanabe, Y.; Kajiyama, H.; Shibata, K.; Ino, K.; Tamakoshi, K.; Hattori, A.; et al. Expression of adipocyte-derived leucine aminopeptidase in endometrial cancer. Association with tumor grade and CA-125. Tumour. Biol. 2003, 24, 203-208.
72. Watanabe, Y.; Shibata, K.; Kikkawa, F.; Kajiyama, H.; Ino, K.; Hattori, A.; Tsujimoto, M.; Mizutani, S. Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system. Clin. Cancer Res. 2003, 9, 6497-6503.
73. Shibata, K.; Kikkawa, F.; Mizokami, Y.; Kajiyama, H.; Ino, K.; Nomura, S.; Mizutani, S. Possible involvement of adipocyte-derived leucine aminopeptidase via angiotensin II in endometrial carcinoma. Tumour. Biol. 2005, 26, 9-16.
74. Mehta, A.M.; Jordanova, E.S.; Kenter, G.G.; Ferrone, S.; Fleuren, G.J. Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol. Immunother. 2008, 57, 197-206.
75. Cifaldi, L.; Lo Monaco, E.; Forloni, M.; Giorda, E.; Lorenzi, S.; Petrini, S.; Tremante, E.; Pende, D.; Locatelli, F.; Giacomini, P.; et al. Natural killer cells efficiently reject lymphoma silenced for the endoplasmic reticulum aminopeptidase associated with antigen processing. Cancer Res. 2011, 71, 1597-1606.