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. 1990 Aug;87(15):5658–5662. doi: 10.1073/pnas.87.15.5658

Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins.

R G Maki 1, L J Old 1, P K Srivastava 1
PMCID: PMC54386  PMID: 2377606

Abstract

Cell-surface glycoproteins of 96 kDa (gp96) have been implicated in immunogenicity of methylcholanthrene-induced mouse sarcomas in syngeneic hosts. In view of the potential immunogenicity of gp96-related molecules in human tumors, we have defined the 5'-regulatory and complete coding regions of a human gp96 transcript. The 5'-regulatory region contains an imperfect heat shock element apart from other regulatory sequences. The amino acid sequence of human gp96 is 96% homologous to its murine counterpart and genes for the two molecules show significant homology between untranslated regions. Comparison of gp96 sequences to other sequences in DNA and protein data bases indicates significant homology with the stress proteins 94-kDa glucose-regulated protein (grp94) and 108-kDa heat shock protein (hsp108) and 99-kDa endoplasmic reticular protein (ERp99). These molecules are either identical or represent a family of closely related molecules. With regard to their role in tumor immunity, it needs to be determined whether gp96 molecules are tumor antigens per se or whether they serve as carriers of other immunogenic moieties.

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Selected References

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  1. Anichini A., Fossati G., Parmiani G. Clonal analysis of cytotoxic T-lymphocyte response to autologous human metastatic melanoma. Int J Cancer. 1985 May 15;35(5):683–689. doi: 10.1002/ijc.2910350518. [DOI] [PubMed] [Google Scholar]
  2. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  3. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  4. Boon T., Van Pel A., De Plaen E. Tum- transplantation antigens, point mutations, and antigenic peptides: a model for tumor-specific transplantation antigens? Cancer Cells. 1989 Sep;1(1):25–28. [PubMed] [Google Scholar]
  5. Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [DOI] [PubMed] [Google Scholar]
  6. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chang S. C., Erwin A. E., Lee A. S. Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors. Mol Cell Biol. 1989 May;9(5):2153–2162. doi: 10.1128/mcb.9.5.2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Plaen E., Lurquin C., Van Pel A., Mariamé B., Szikora J. P., Wölfel T., Sibille C., Chomez P., Boon T. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum- antigen P91A and identification of the tum- mutation. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2274–2278. doi: 10.1073/pnas.85.7.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Geetha-Habib M., Noiva R., Kaplan H. A., Lennarz W. J. Glycosylation site binding protein, a component of oligosaccharyl transferase, is highly similar to three other 57 kd luminal proteins of the ER. Cell. 1988 Sep 23;54(7):1053–1060. doi: 10.1016/0092-8674(88)90120-1. [DOI] [PubMed] [Google Scholar]
  10. Hearing V. J., Gersten D. M., Montague P. M., Vieira W. D., Galetto G., Law L. W. Murine melanoma-specific tumor rejection activity elicited by a purified, melanoma-associated antigen. J Immunol. 1986 Jul 1;137(1):379–384. [PubMed] [Google Scholar]
  11. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  12. Höller M., Westin G., Jiricny J., Schaffner W. Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated. Genes Dev. 1988 Sep;2(9):1127–1135. doi: 10.1101/gad.2.9.1127. [DOI] [PubMed] [Google Scholar]
  13. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  14. Knuth A., Danowski B., Oettgen H. F., Old L. J. T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3511–3515. doi: 10.1073/pnas.81.11.3511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knuth A., Wölfel T., Klehmann E., Boon T., Meyer zum Büschenfelde K. H. Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2804–2808. doi: 10.1073/pnas.86.8.2804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Konno A., Sato N., Yagihashi A., Torigoe T., Cho J. M., Torimoto K., Hara I., Wada Y., Okubo M., Takahashi N. Heat- or stress-inducible transformation-associated cell surface antigen on the activated H-ras oncogene-transfected rat fibroblast. Cancer Res. 1989 Dec 1;49(23):6578–6582. [PubMed] [Google Scholar]
  17. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kulomaa M. S., Weigel N. L., Kleinsek D. A., Beattie W. G., Conneely O. M., March C., Zarucki-Schulz T., Schrader W. T., O'Malley B. W. Amino acid sequence of a chicken heat shock protein derived from the complementary DNA nucleotide sequence. Biochemistry. 1986 Oct 7;25(20):6244–6251. doi: 10.1021/bi00368a061. [DOI] [PubMed] [Google Scholar]
  19. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  20. Mazzarella R. A., Green M. ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum, is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa glucose regulated protein (GRP94). J Biol Chem. 1987 Jun 25;262(18):8875–8883. [PubMed] [Google Scholar]
  21. Moore S. K., Kozak C., Robinson E. A., Ullrich S. J., Appella E. Cloning and nucleotide sequence of the murine hsp84 cDNA and chromosome assignment of related sequences. Gene. 1987;56(1):29–40. doi: 10.1016/0378-1119(87)90155-7. [DOI] [PubMed] [Google Scholar]
  22. Mukherji B., MacAlister T. J. Clonal analysis of cytotoxic T cell response against human melanoma. J Exp Med. 1983 Jul 1;158(1):240–245. doi: 10.1084/jem.158.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Munro S., Pelham H. R. An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell. 1986 Jul 18;46(2):291–300. doi: 10.1016/0092-8674(86)90746-4. [DOI] [PubMed] [Google Scholar]
  24. Old L. J. Cancer immunology: the search for specificity--G. H. A. Clowes Memorial lecture. Cancer Res. 1981 Feb;41(2):361–375. [PubMed] [Google Scholar]
  25. Real F. X., Furukawa K. S., Mattes M. J., Gusik S. A., Cordon-Cardo C., Oettgen H. F., Old L. J., Lloyd K. O. Class 1 (unique) tumor antigens of human melanoma: identification of unique and common epitopes on a 90-kDa glycoprotein. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3965–3969. doi: 10.1073/pnas.85.11.3965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Russel M., Kidd S., Kelley M. R. An improved filamentous helper phage for generating single-stranded plasmid DNA. Gene. 1986;45(3):333–338. doi: 10.1016/0378-1119(86)90032-6. [DOI] [PubMed] [Google Scholar]
  27. Sorger P. K., Pelham H. R. The glucose-regulated protein grp94 is related to heat shock protein hsp90. J Mol Biol. 1987 Mar 20;194(2):341–344. doi: 10.1016/0022-2836(87)90380-9. [DOI] [PubMed] [Google Scholar]
  28. Srinivas U. K., Revathi C. J., Das M. R. Heat-induced expression of albumin during early stages of rat embryo development. Mol Cell Biol. 1987 Dec;7(12):4599–4602. doi: 10.1128/mcb.7.12.4599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Srivastava P. K., Chen Y. T., Old L. J. 5'-structural analysis of genes encoding polymorphic antigens of chemically induced tumors. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3807–3811. doi: 10.1073/pnas.84.11.3807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Srivastava P. K., DeLeo A. B., Old L. J. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci U S A. 1986 May;83(10):3407–3411. doi: 10.1073/pnas.83.10.3407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Srivastava P. K., Old L. J. Identification of a human homologue of the murine tumor rejection antigen GP96. Cancer Res. 1989 Mar 15;49(6):1341–1343. [PubMed] [Google Scholar]
  32. Srivastava P. K., Old L. J. Individually distinct transplantation antigens of chemically induced mouse tumors. Immunol Today. 1988 Mar;9(3):78–83. doi: 10.1016/0167-5699(88)91269-8. [DOI] [PubMed] [Google Scholar]
  33. Swaroop A., Weissman S. M. Charon BS(+) and (-), versatile lambda phage vectors for constructing directional cDNA libraries and their efficient transfer to plasmids. Nucleic Acids Res. 1988 Sep 12;16(17):8739–8739. doi: 10.1093/nar/16.17.8739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Topalian S. L., Solomon D., Rosenberg S. A. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol. 1989 May 15;142(10):3714–3725. [PubMed] [Google Scholar]
  35. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  36. Ullrich S. J., Robinson E. A., Law L. W., Willingham M., Appella E. A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc Natl Acad Sci U S A. 1986 May;83(10):3121–3125. doi: 10.1073/pnas.83.10.3121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Young R. A., Elliott T. J. Stress proteins, infection, and immune surveillance. Cell. 1989 Oct 6;59(1):5–8. doi: 10.1016/0092-8674(89)90861-1. [DOI] [PubMed] [Google Scholar]
  38. Zagouras P., Rose J. K. Carboxy-terminal SEKDEL sequences retard but do not retain two secretory proteins in the endoplasmic reticulum. J Cell Biol. 1989 Dec;109(6 Pt 1):2633–2640. doi: 10.1083/jcb.109.6.2633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. de Vries J. E., Spits H. Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity. J Immunol. 1984 Jan;132(1):510–519. [PubMed] [Google Scholar]
  40. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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