Abstract
Evi27 is a common site of retroviral integration in BXH2 murine myeloid leukemias. Here we show that integration at Evi27 occurs in a CpG island ∼6 kb upstream from a novel gene (designated Evi27) with homology to the IL17 receptor (Il17r) and that proviral integrations result in increased expression of the Evi27 protein on the cell surface. The human EVI27 homolog was also cloned and mapped to chromosome 3p21. Multiple Evi27 isoforms were detected at the RNA and protein level in both human and mouse, indicating that Evi27 expression is complex. Some of the isoforms are shown to likely represent secreted soluble forms of the protein produced by intron incorporation or by proteolytic cleavage. In the mouse, highest Evi27 expression occurs in liver and testes with lower expression in kidney and lung. In humans, EVI27 is expressed at high levels in the kidney, with moderate levels in the liver, brain, and testes. Within hematopoietic cells, Evi27 expression is restricted. Northern and Western analysis showed that Evi27 is expressed in selected T-cell, B-cell and myeloid cell lines. These results suggest that Evi27 expression is tightly regulated during hematopoietic differentiation. Collectively, these studies identify a new member of the cytokine receptor family whose increased and uncoordinated expression may lead to myeloid leukemia by altering Evi27's normal ability to control the growth and/or differentiation of hematopoietic cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bagby GC . 1994 The Molecular Basis of Blood Diseases Stamatoyannopoulos G, Nienhuis AW, Majerus PW and Varmus H eds. WB Saunders Press Philadelphia pp 71–106
Baumbach WR, Colston EM and Cole MD . 1988 J Virol 62: 3151–3155
Bedigian HG, Johnson DA, Jenkins NA, Copeland NG and Evans R . 1984 J Virol 51: 586–594
Benton WD and Davis RW . 1977 Science 196: 180–182
Blankenstein T, Qin ZH, Li WQ and Diamantstein T . 1990 J Exp Med 171: 965–970
Buchburg AM, Bedigian HG, Jenkins NA and Copeland NA . 1990 Mol Cell Biol 10: 4658–4666
Chretien S, Moreau-Gachelin F, Apiou F, Courtois G, Mayeux P, Dutrillaux B, Cartron JP, Gisselbrecht S and Lacombe C . 1997 Blood 83: 1813–1821
Copeland NG, Jenkins NA, Gilbert DJ, Eppig JT, Maltais LJ, Miller JC, Dietrich WF, Weaver A, Lincoln SE, Steen RG, Stein LD, Nadeau JH and Lander ES . 1993 Science 262: 57–66
Copeland NG and Jenkins NA . 1999 Myeloid leukemia disease genes and mouse models In Animal Models of Cancer Predisposition Syndromes Hiai H and Hino O eds Karger Press Basel pp53–63
Flubacher MM, Bear SE and Tsichlis PN . 1994 J Virol 68: 7709–7716
Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S, Blanchard D, Gaillard C, Das Mahapatra B, Rouvier E, Golstein P, Banchereau J and Lebecque S . 1996 J Exp Med 183: 2593–2603
Gilbert DJ, Neumann PE, Taylor BA, Jenkins NA and Copeland NG . 1993 J Virol 67: 2083–2090
Gisselbrecht S, Fichelson S, Sola B, Bordereaux D, Hampe A, Andre C, Galibert F and Tambourin P . 1987 Nature 329: 259–261
Heaney ML and Golde DW . 1996 Blood 87: 847–857
Hino M, Tojo A, Misawa Y, Morii H, Takaku F and Shibuya M . 1991 Mol Cell Biol 11: 5527–5533
Jackson TR, Blair LA, Marshall J, Goedert M and Hanley MR . 1988 Nature 335: 437–440
Jenkins NA, Copeland NG, Taylor BA, Bedigian HG and Lee BK . 1982 J Virol 42: 379–388
Johansson B, Billstrom R, Kristoffersson U, Akerman M, Garwicz S, Ahlgren T, Malm C and Mitelman F . 1997 Leukemia 11: 1207–1213
Kennedy J, Rossi DL, Zurawski SM, Vega Jr F, Kastelein RA, Wagner JL, Hannum CH and Zlotnik A . 1996 J Interferon Cytokine Res 16: 611–617
Largaespada DA, Shaughnessy Jr JD, Jenkins NA and Copeland NG . 1995 J Virol 69: 5095–5102
Li H, Chen J, Huang A, Stinson J, Heldens S, Foster J, Dowd P, Gurney AL and Wood WI . 2000 Proc Natl Acad Sci USA 97: 773–778
Li J, Shen H, Himmel K, Dupuy A, Largaespada D, Nakamura T, Shaughnessy J, Jenkins N and Copeland N . 1999 Nat Genet 23: 348–353
Liao X, Du Y, Morse III HC, Jenkins NA and Copeland NG . 1997 Oncogene 14: 1023–1029
Look AT . 1997 Science 278: 1059–1064
Morishita K, Parker DS, Mucenski ML, Jenkins NA, Copeland NG and Ihle JN . 1988 Cell 54: 831–840
Nakai K and Kanehisa M . 1992 Genomics 14: 897–911
Nakamura T, Largaespada DA, Shaughnessy Jr JD, Jenkins NA and Copeland NG . 1996a Nat Genet 12: 149–153
Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen I-M, Feinberg AP, Jenkins NA, Copeland NG and Shaughnessy Jr JD . 1996b Nat Genet 12: 154–158
Ogawa S, Kurokawa M, Tanaka T, Mitani K, Inazawa J, Hangaishi A, Tanaka K, Matsuo Y, Minowada J, Tsubota T, Yazaki Y and Hirai H . 1996 Oncogene 13: 183–191
Penciolelli JF, Wendling F, Robert-Lezenes J, Barque JP, Tambourin P and Gisselbrecht S . 1987 J Virol 61: 579–583
Roberts T, Chernova O and Cowell JK . 1998 Hum Mol Genet 7: 1169–1178
Rouvier E, Luciani MF, Mattei MG, Denizot F and Golstein P . 1993 J Immunol 150: 5445–5456
Sambrook J, Fritsch EF and Maniatis T . 1989 Molecular Cloning A Laboratory Manual Cold Spring Harbor Laboratory Press New York
Schwarzenberger P, La Russa V, Miller A, Ye P, Huang W, Zieske A, Nelson S, Bagby GJ, Stoltz D, Mynatt RL, Spriggs M and Kolls JK . 1998 J Immunol 161: 6383–6389
Shaughnessy Jr JD, Largaespada DA, Tian E, Fletcher CF, Cho BC, Vyas P, Jenkins NA and Copeland NG . 1999 Oncogene 18: 2069–2084
Shi G, Weh HJ, Martensen S, Seeger D and Hossfeld DK . 1996 Cytogenet Cell Genet 74: 295–299
Souyri M, Vigon I, Penciolelli JF, Heard JM, Tambourin P and Wendling F . 1990 Cell 63: 1137–1147
Sugita T, Totsuka T, Saito M, Yamasaki K, Taga T, Hirano T and Kishimoto T . 1990 J Exp Med 171: 2001–2009
Viskochil D, Buchberg AM, Xu G, Cawthorn RM, Stevens J, Wolff RK, Culver M, Carey JC, Copeland NG, Jenkins NA, White R and O'Connell P . 1990 Cell 62: 187–192
van den Berg A, Dijkuizen T, Draaijers TG, Hulsbeek MM, Maher ER, van den Berg E, Storkel S and Buys CH . 1997 Genes Chromosomes Cancer 19: 228–232
Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, Cohen JI and Spriggs MK . 1995a Immunity 3: 811–821
Yao Z, Painter SL, Fanslow WC, Ulrich D, Macduff BM, Spriggs MK and Armitage RJ . 1995b J Immunol 155: 5483–5486
Yao Z, Spriggs MK, Derry JM, Strockbine L, Park LS, VandenBos T, Zappone JD, Painter SL and Armitage RJ . 1997 Cytokine 9: 794–800
Young D, Waitches G, Birchmeier C, Fasano O and Wigler M . 1986 Cell 45: 711–719
Ymer S, Tucker WQ, Sanderson CJ, Hapel AJ, Campbell HD and Young IG . 1985 Nature 317: 255–258
Acknowledgements
We thank Diane E Hasz for technical assistance. This research was sponsored in part by the National Cancer Institute, DHHS, under contract with ABL.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tian, E., Sawyer, J., Largaespada, D. et al. Evi27 encodes a novel membrane protein with homology to the IL17 receptor. Oncogene 19, 2098–2109 (2000). https://doi.org/10.1038/sj.onc.1203577
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203577
Keywords
This article is cited by
-
IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte
Respiratory Research (2023)
-
Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer
Scientific Reports (2016)
-
Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-κB-mediated antiapoptotic pathway
Oncogene (2014)
-
Codon optimization, expression, purification, and functional characterization of recombinant human IL-25 in Pichia pastoris
Applied Microbiology and Biotechnology (2013)
-
The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex
BMC Pulmonary Medicine (2011)