Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Feb;91(2):239–247. doi: 10.1111/j.1349-7006.2000.tb00937.x

Mouse Homologue of the Human SART3 Gene Encoding Tumor‐rejection Antigen

Kenji Harada 1, Akira Yamada 1,2,, Takashi Mine 2, Nobutoshi Kawagoe 1, Hideo Takasu 1, Kyogo Itoh 1,2
PMCID: PMC5926322  PMID: 10761712

Abstract

We recently isolated a human SART3 (hSART3) gene encoding a tumor‐rejection antigen recognized by HLA‐A2402‐restricted cytotoxic T lymphocytes (CTLs). The hSART3 was also found to exist as an RNA‐binding nuclear protein of unknown biological function. In this study, we cloned and analyzed the homologous mouse SART3 (mSART3) gene in order to understand better the function of hSART3, and to aid in establishing animal models of specific immunotherapy. The cloned 3586‐bp cDNA encoded a 962‐amino acid polypeptide with high homology to hSART3 (80% or 86% identity at the nucleotide or protein level, respectively). Nonapeptides recognized by the HLA‐A2402‐restricted CTLs and all of the RNA‐binding motifs were conserved between hSART3 and mSART3. The mSART3 mRNA was ubiquitously expressed in normal tissues, with low level expression in the liver, heart, and skeletal muscle. It was widely expressed in various organs from as early as day 7 of gestation. mSART3 was mapped to chromosome 5, a syntenic region for human chromosome 12q23–24, and its genomic DNA extended over 28‐kb and consisted of 19 exons. This information should be important for studies of the biological functions of the SART3 protein and for the establishment of animal models of specific cancer immunotherapy.

Keywords: SART3, Tumor‐rejection antigen, RNA‐binding protein, HLA‐A2402, Cytotoxic T lymphocytes

Full Text

The Full Text of this article is available as a PDF (278.3 KB).

REFERENCES

  • 1. ) Boon , T. and van der Bruggen , P.Human tumor antigens recognized by T lymphocytes . J. Exp. Med. , 183 , 725 – 729 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) van der Bruggen , P. , Traversari , C. , Chomez , P. , Lurquin , C. , De Plaen , E. , Van den Eynde , B. , Knuth , A. and Boon , T.A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma . Science , 254 , 1643 – 1647 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Rosenberg , S. A. , Yang , J. C. , Schwartzentruber , D. J. , Hwu , P. , Marincola , F. M. , Topalian , S. L. , Restifo , N. P. , Dudley , M. E. , Schwarz , S. L. , Spiess , P. J. , Wunderlich , J. R. , Parkhurst , M. R. , Kawakami , Y. , Seipp , C. A. , Einhorn , J. H. and White , D. E.Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patient with metastatic melanoma . Nat. Med. , 4 , 321 – 327 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. ) Nestle , F. O. , Alijagic , S. , Gilliet , M. , Sun , Y. , Grabbe , S. , Dummer , R. , Burg , G. and Schadendorf , D.Vaccination of melanoma patients with peptide‐ or tumor lysate‐pulsed dendritic cells . Nat. Med. , 4 , 328 – 332 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Yang , D. , Nakao , M. , Shichijo , S. , Sasatomi , T. , Takasu , H. , Matsumoto , H. , Mori , K. , Hayashi , A. , Yamana , H. , Shirouzu , K. and Itoh , K.Identification of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA‐A24‐restricted cytotoxic T lymphocytes in cancer patients . Cancer Res. , 59 , 4056 – 4063 ( 1999. ). [PubMed] [Google Scholar]
  • 6. ) Hicks , G. R. and Raikhel , N. V.Protein import into the nucleus: an integrated view . Annu. Rev. Cell Dev. Biol. , 11 , 15 – 188 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Christopher , G. B. and Gideon , D.Conserved structures and diversity of functions of RNA‐binding proteins . Science , 265 , 615 – 621 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Patschinsky , T. , Hunter , T. , Esch , F. S. , Cooper , J. A. and Sefton , B. M.Analysis of the sequence of amino acids surrounding sites of tyrosine phosphorylation . Proc. Natl. Acad. Sci. USA , 79 , 973 – 977 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Gu , J. , Shimba , S. , Nomura , N. and Reddy , R.Isolation and characterization of a new 110 kDa human nuclear RNA‐binding protein (p110nrb) . Biochim. Biophys. Acta , 1399 , 1 – 9 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Chomczynski , P. and Sacchi , N.Single‐step method of RNA isolation by acid guanidinium thiocyanate‐phenolchloroform extraction . Anal. Biochem. , 162 , 156 – 159 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Kozak , M.Bifunctional messenger RNAs in eukaryotes . Cell , 47 , 481 – 483 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Kozak , M.Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in position +5 and +6 . EMBO J. , 16 , 2482 – 2492 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Swimmer , C. and Shenk , T.Selection of sequence elements that substitute for the standard AATAAA motif which signals 3′ processing and polyadenylation of late simian virus 40 mRNAs . Nucleic Acids Res. , 13 , 8053 – 8063 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Petschek , J. P. , Mermer , M. J. , Scheckelhoff , M. R. , Simone , A. A. and Vaughn , J. C.RNA editing in Drosophila 4f‐rnp gene nuclear transcripts by multiple A‐to‐G conversions . J. Mol. Biol. , 259 , 885 – 890 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Petschek , J. P. , Scheckelhoff , M. R. , Mermer , M. J. and Vaughn , J. C.RNA editing and alternative splicing generate mRNA transcript diversity from the Drosophila 4f‐rnp locus . Gene , 204 , 267 – 276 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Ma , K. , Inglis , J. D. , Sharkey , A. , Bickmore , W. A. , Hill , R. E. , Prosser , E. J. , Speed , R. M. , Thomson , K. T. , Jobling , M. , Taylor , K. , Wolfe , J. , Cooke , H. J. , Hargreave , T. B. and Chandley , A. C.A Y chromosome gene family with RNA‐binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis . Cell , 75 , 1287 – 1295 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Mizrachi‐Karsch , I. and Haynes , S. R.The Rb97D gene encodes a potential RNA‐binding protein required for spermatogenesis in Drosophila . Nucleic Acids Res. , 21 , 2229 – 2235 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Baker , B. S.Sex in flies: the splice of life . Nature , 340 , 521 – 524 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Hodgkin , J.Drosophila sex determination: a cascade of regulated splicing . Cell , 56 , 905 – 906 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Kelly , R. L.Initial organization of the Drosophila dorsoventral axis depends on an RNA‐binding protein encoded by the squid gene . Genes Dev. , 7 , 948 – 960 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Matunis , E. L. , Kelly , R. and Dreyfuss , G.Essential role for a heterogeneous nuclear ribonucleoprotein (hnRNP) in oogenesis: hrp40 is absent from the germ line in dorsoventral mutant squid . Proc. Natl. Acad. Sci. USA , 91 , 2781 – 2784 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. ) Robinow , S. , Campos , A. R. , Yao , K. M. and White , K.The elav gene product of Drosophila, required in neurons, has three RNP consensus motifs . Science , 242 , 1570 – 1572 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Chambers , J. C. , Kenan , D. , Martin , B. J. and Keene , J. D.Genomic structure and amino acid sequence domains of the human La autoantigen . J. Biol. Chem. , 263 , 18043 – 18051 ( 1988. ). [PubMed] [Google Scholar]
  • 24. ) Deutscher , S. L. , Harley , J. B. and Keene , J. D.Molecular analysis of the 60‐kDa human Ro ribonucleoprotein . Proc. Natl. Acad. Sci. USA , 85 , 9479 – 9483 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Deutscher , S. L. and Keene , J. D.A sequence‐specific conformational epitope on U1 RNA is recognized by a unique autoantibody . Proc. Natl. Acad. Sci. USA , 85 , 3299 – 3303 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. ) Steiner , G. , Hartmuth , K. , Skriner , K. , Maurer‐Fogy , I. , Sinski , A. , Thalmann , E. , Hassfeld , W. , Barta , A. and Smolen , J. S.Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex . J. Clin. Invest. , 90 , 1061 – 1066 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Szabo , A. , Dalmanu , J. , Manley , G. , Rosenfeld , M. , Wong , E. , Henson , J. , Posner , J. B. and Furneaux , H. M.HuD, a paraneoplastic encephalomyelitis antigen, contains RNA‐binding domains and is homologous to Elav and Sex‐lethal . Cell , 67 , 325 – 333 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Soulard , M. , Della Valle , V. , Siomi , M. C. , Piñol‐Roma , S. , Codogno , P. , Bauvy , C. , Bellini , M. , Lacroix , J. C. , Monad , G. , Dreyfuss , G. and Larsen , C. J.hnRNP G: sequence and chracterization of a glycosylated RNA‐binding protein . Nucleic Acids Res. , 21 , 4210 – 4217 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. ) Miyachi , K. , Fritzler , M. J. and Tan , E. M.Autoantibody to a nuclear antigen in proliferating cells . J. Immunol. , 121 , 2228 – 2234 ( 1978. ). [PubMed] [Google Scholar]
  • 30. ) Bravo , R. , Frank , R. , Blundell , P. A. and Macdonald‐Bravo , H.Cyclin/PCNA is the auxiliary protein of DNA polymerase‐δ . Nature , 326 , 515 – 517 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Chan , E. K. , Imai , H. , Hamel , J. C. and Tan , E. M.Human autoantibody to RNA polymerase I transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR‐90 and ribosomal RNA transcription upstream binding factor . J. Exp. Med. , 174 , 1239 – 1244 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. ) Gottlieb , E. and Steitz , J. A.Function of the mammalian La protein: evidence for its action in transcription termination by RNA polymerase III . EMBO J. , 8 , 851 – 861 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. ) Reimer , G. , Rose , K. M. , Scheer , U. and Tan , E. M.Autoantibody to RNA polymerase I in scleroderma sera . J. Clin. Invest. , 79 , 65 – 72 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. ) Lerner , M. R. and Steitz , J. A.Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus . Proc. Natl. Acad. Sci. USA , 76 , 5495 – 5497 ( 1979. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. ) Moroi , Y. , Peebles , C. , Fritzler , M. J. and Tan , E. M.Autoantibody to centromere (kinetochore) in scleroderma sera . Proc. Natl. Acad. Sci. USA , 77 , 1627 – 1631 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. ) Brenner , S. , Pepper , D. , Berne , M. E. , Tan , E. M. and Brinkley , B. R.Kinetochore structure, duplication, and distribution in mammalian cells: analysis by human autoantibodies from scleroderma patients . J. Cell Biol. , 91 , 95 – 102 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. ) Earnshaw , W. C. , Sullivan , K. F. , Machlin , P. S. , Cooke , C. A. , Kaiser , D. A. , Pollard , T. D. , Rothfield , N. F. and Cleveland , D. W.Molecular cloning of cDNA for CENPB, the major human centromere autoantigen . J. Cell Biol. , 104 , 817 – 829 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. ) Burnham , T. K.Antinuclear antibodies in patients with malignancies . Lancet , ii , 2436 – 2437 ( 1972. ). [DOI] [PubMed] [Google Scholar]
  • 39. ) Pupa , S. M. , Menard , S. , Andreola , S. and Colnaghi , M.Antibody response against the c‐erbB‐2 oncoprotein in breast carcinoma patients . Cancer Res. , 53 , 5864 – 5866 ( 1993. ). [PubMed] [Google Scholar]
  • 40. ) Winter , S. F. , Minna , J. D. , Johnson , B. E. , Takahashi , T. , Gazder , F. and Carbone , D. P.Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation . Cancer Res. , 52 , 4168 – 4174 ( 1992. ). [PubMed] [Google Scholar]
  • 41. ) Houghton , A. N.Cancer antigens: immune recognition of self and altered self . J. Exp. Med. , 180 , 1 – 4 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. ) Sahin , U. , Türeci , Ö. , Schmitt , H. , Cochlovius , B. , Johannes , T. , Schmits , R. , Stenner , F. , Luo , G. , Schobert , I. and Pfreundschuh , M.Human neoplasms elicit multiple specific immune responses in the autologous host . Proc. Natl. Acad. Sci. USA , 92 , 11810 – 11813 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. ) Old , L. J. and Chen , Y.‐T.New paths in human cancer serology . J. Exp. Med. , 187 , 1163 – 1167 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. ) Shichijo , S. , Nakao , M. , Imai , Y. , Takasu , H. , Kawamoto , M. , Niiya , F. , Yang , D. , Toh , Y. , Yamana , H. and Itoh , K.A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes . J. Exp. Med. , 187 , 277 – 288 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. ) Valenta , R. , Natter , S. , Seiberler , S. , Wichlas , S. , Maurer , D. , Hess , M. , Pavelka , M. , Grote , M. , Ferreira , F. , Szepfalusi , Z. , Valent , P. and Sting , G.Molecular characterization of an autoantigen, Hom s 1, identified by serum IgE from atopic dermatitis patients . J. Invest. Dermatol. , 111 , 1178 – 1183 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 46. ) Corydon , M. J. , Andresen , B. S. , Bross , P. , Kjeldsen , M. , Andreasen , P. H. , Eiberg , H. , Kolvraa , S. and Gregersen , N.Structural organization of the human short‐chain acyl‐CoA dehydrogenase gene . Mamm. Genome , 8 , 922 – 926 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 47. ) Schiffer , S. P. , Prochazka , M. , Jezyk , P. F. , Roderick , T. H. , Yudkoff , M. and Patterson , D. F.Organic aciduria and butyryl CoA dehydrogenase deficiency in BALB/cByJ mice . Biochem. Genet. , 27 , 47 – 58 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 48. ) Bach , I. , Galcheva‐Gargova , Z. , Mattei , M.‐G. , Simon‐Chazottes , D. , Guenet , J.‐L. , Cereghini , S. and Yaniv , M.Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse . Genomics , 8 , 155 – 164 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 49. ) Turnbull , D. M. , Bartlett , K. , Stevens , D. L. , Alberti , K. G. M. M. , Gibson , G. J. , Johnson , M. A. , McCulloch , A. J. and Sherratt , H. S. A.Short‐chain acyl‐CoA dehydrogenase deficiency associated with a lipid‐storage myopathy and secondary carnitine deficiency . N. Engl. J. Med. , 311 , 1232 – 1236 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 50. ) Woo , S. L. , Lidsky , A. S. , Guttler , F. , Chandra , T. and Robson , K. J.Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria . Nature , 306 , 151 – 155 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 51. ) Lidsky , A. S. , Robson , K. J. , Thirumalachary , C. , Barker , P. E. , Ruddle , F. H. and Woo , S. L.The PKU locus in man is on chromosome 12 . Am. J. Hum. Genet. , 36 , 527 – 533 ( 1984. ). [PMC free article] [PubMed] [Google Scholar]
  • 52. ) Polymeropoulos , M. H. , Ide , S. E. , Magyari , T. and Francomano , C. A.Brachydactyly type C gene maps to human chromosome 12q24 . Genomics , 38 , 45 – 50 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 53. ) Jamieson , C. R. , van der Burgt , I. , Brady , A. F. , van Reen , M. , Elsawi , M. M. , Hol , F. , Jeffery , S. , Patton , M. A. and Mariman , E.Mapping a gene for Noonan syndrome to the long arm of chromosome 12 . Nat. Genet. , 8 , 357 – 360 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 54. ) van der Vleuten , A. J. W. , van Ravenswaaij‐Arts , C. M. A. , Frijns , C. J. M. , Smits , A. P. T. , Hageman , G. , Padberg , G. W. and Kremer , H.Localization of the gene for a dominant congenital spinal muscular atrophy predominantly affecting the lower limbs to chromosome 12q23–24 . Eur. J. Hum. Genet. , 6 , 376 – 382 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 55. ) Timmerman , V. , De Jonghe , P. , Simokovic , S. , Lofgren , A. , Beuten , J. , Nelis , E. , Ceuterick , C. , Martin , J. J. and Van Broeckhoven , C.Distal hereditary motor neuropathy type II (distal HMN II): mapping of a locus to chromosome 12q24 . Hum. Mol. Genet. , 5 , 1065 – 1069 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 56. ) Isozumi , K. , DeLong , R. , Kaplan , J. , Deng , H.‐X. , Iqbal , Z. , Hung , W.‐Y. , Wilhelmsen , K. C. , Hentati , A. , Pericak‐Vance , M. A. and Siddique , T.Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1–q24.31 . Hum. Mol. Genet. , 5 , 1377 – 1382 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 57. ) Mitelman , F. , Mertens , F. and Johansson , B.A breakpoint map of recurrent chromosomal rearrangements in human neoplasia . Nat. Genet. , 15 , 417 – 474 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 58. ) Marchand , M. , van Baren , N. , Weynants , P. , Brichard , V. , Dréno , B. , Tessier , M.‐H. , Rankin , E. , Parmiani , G. , Arienti , F. , Humblet , Y. , Bourlond , A. , Vanwijck , R. , Liénard , D. , Beauduin , M. , Dietrich , P.‐Y. , Russo , V. , Kerger , J. , Masucci , G. , Jäger , E. , de Greve , J. , Atzpodien , J. , Brasseur , F. , Coulie , P. G. , van der Bruggen , P. and Boon , T.Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE‐3 and presented by HLA‐A1 . Int. J. Cancer , 80 , 219 – 230 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 59. ) Ibe , M. , Moore , Y. I. , Miwa , K. , Kaneko , Y. , Yokota , S. and Takiguchi , M.Role of strong anchor residues in the effective binding of 10‐mer and 11‐mer peptides to HLA‐A2402 molecules . Immunogenetics , 44 , 233 – 241 ( 1996. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES