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Gene Review

Mela  -  melanoma antigen

Mus musculus

Synonyms: 80kDa, Ag, env, gag, gag-pol, ...
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Disease relevance of Mela

  • We have isolated a cDNA (H52) of 2.8-kb-long encoding an 80-kDa mouse melanoma Ag that is defined by a syngeneic anti-B16 melanoma mAb with an ability to block anti-melanoma cytotoxic T cell responses [1].
  • Nucleotide sequence analysis has clearly demonstrated that H52 cDNA encodes the full length of the env gene and long terminal repeat region of endogenous ecotropic murine leukemia provirus of AKV-type, which is defective in C57BL/6 [1].
  • We have now determined the nucleotide sequence of the archetypal Set 2 clone, pAG59, and can thus identify it as corresponding to the env gene of the endogenous, ecotropic C-type retrovirus of Balb/c mice, Emv-1 [2].
  • Fragment exchange between the XC-negative molecular clone p110 and the XC-positive AKR virus clone p623 revealed that the defect in p110 lies 3' of the SalI site located in the pol region [3].
  • The pol (for polymerase) gene of the murine leukemia viruses (MuLVs) is expressed in the form of a large Gag-Pol precursor protein by the suppression of translational termination, or enhanced readthrough, of a UAG stop codon at the end of gag [4].

High impact information on Mela

  • The structure of several of the abundant transcripts demonstrates further that they are transcribed from independent defective endogenous proviral genomes exhibiting extensive deletions of env coding regions as well as modified U3 regions distinct from those found in exogenous retroviral transcripts [5].
  • The 4026 nucleotide long FBJ-MuSV proviral DNA contains two long terminal repeats, a substitution of 1639 nucleotides of mouse cellular DNA (v-fos) and the 3' end of the env gene derived from FBJ-MuLV [6].
  • Short interspersed repetitive DNA elements in eucaryotes: transposable DNA elements generated by reverse transcription of RNA pol III transcripts [7]?
  • We therefore conclude that although U6 RNA genes appear to be transcribed by pol III, they are preceeded by an enhancer-like element which can functionally substitute for the enhancer of a pol II-transcribed U RNA gene [8].
  • To examine more closely the role of gp70 in the CTL response to MuLV infections, we have constructed murine cell lines which express only the env gene of the Moloney murine leukaemia virus (M-MuLV) [9].

Chemical compound and disease context of Mela

  • Of these, at least 400-500 base pairs located near the 5' end of v-fes encode a portion of the GA-FeSV polyprotein; the remaining 1.2 kilobases are derived from the FeLV env gene but do not appear to encode any detectable product related to the FeLV envelope glycoprotein [10].
  • Immunogenic tumor variant clones derived by N-methyl-N'-nitro-N-nitrosoguanidine treatment of Eb lymphoma cells showed structurally altered gp70 env proteins at the cell surface [11].
  • Ag processing and presentation were inhibited by treating the melanoma cells with ammonium chloride [12].
  • Finally, studies of chloroquine inhibition of the capacity of melanoma cells derived from early primary disease to stimulate autologous peripheral blood T cells suggest that such cells process and present tumor-associated Ag in the same fashion as the "model" Ag TT [12].
  • We had previously identified a new family of human endogenous retrovirus-like elements, the HERV-L elements (human endogenous retrovirus with leucine tRNA primer), whose pol gene was most closely related to that of the foamy viruses [13].

Biological context of Mela


Anatomical context of Mela

  • Mitochondria were then isolated by the method of Mela and Seitz (Methods Enzymol.55:39-46; 1979) [17].
  • The Hsp70 peptide-binding domain deletion mutant of the fusion protein was sufficient for inducing Mela-specific cytotoxic T lymphocyte but was not sufficient for engendering potent anti-tumor immunity against B16 [18].
  • Analysis of these hybridomas revealed that clonal frequency of autoreactive B cells specific for RNA pol I are higher in the TSK mice that in the controls. mAbs obtained from the TSK mice were specific for the 190-kD subunit and cross-reacted with Escherichia coli and phage T7 RNA polymerases (155-, 150-, and 107-kD polypeptides) [19].
  • Comparative Northern blot analysis of total type C retroviral gene expression using a gag-pol DNA probe corroborated expression of endogenous type C proviruses in both NOD and NON islet cells and thymus [20].
  • We show that altering the RNA nuclear export element used by HIV gag-pol mRNA from the Rev response element to the constitutive transport element restores both the trafficking of Gag to cellular membranes and efficient HIV assembly in murine cells [21].

Associations of Mela with chemical compounds


Regulatory relationships of Mela


Other interactions of Mela


Analytical, diagnostic and therapeutic context of Mela

  • Our results show that class I H-2 transplantation antigens have a directive influence in determining the antigenicity of proteins encoded by the gag and env MuLV genes [30].
  • Immunoprecipitation of viral-encoded proteins in helper virus-free tumor cell lines detected the P160 Ab-MuLV-transforming protein; however, no trace of the gag, pol, and env helper virus-encoded proteins was found [31].
  • The hybridisation of Western blots with dystrophin antibodies also identifies a protein of approximately 80kDa of variable abundance in different human and mdx tissues [32].
  • The MAGE genes were initially isolated from different kinds of tumors, and based on their virtually exclusive tumor-specific expression in adult tissues, they have been used as targets for cancer immunotherapy [33].
  • DIM tissues were shown to be free of exogenous MMTV inasmuch as Southern blot analysis of DNAs extracted from DIM preneoplasms and tumors showed the lack of a PstI-generated 4.2-kilobase MMTV-gag-pol band [34].


  1. Molecular cloning and characterization of the gene encoding mouse melanoma antigen by cDNA library transfection. Hayashi, H., Matsubara, H., Yokota, T., Kuwabara, I., Kanno, M., Koseki, H., Isono, K., Asano, T., Taniguchi, M. J. Immunol. (1992) [Pubmed]
  2. Activation of endogenous retroviral transcription in SV40-transformed mouse cells. Timmons, P.M., Brickell, P.M., Latchman, D.S., Rigby, P.W. Nucleic Acids Res. (1991) [Pubmed]
  3. A single point mutation in the envelope gene is responsible for replication and XC fusion deficiency of the endogenous ecotropic C3H/He murine leukemia virus and for its repair in culture. Sithanandam, G., Rapp, U.R. J. Virol. (1988) [Pubmed]
  4. Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination. Orlova, M., Yueh, A., Leung, J., Goff, S.P. Cell (2003) [Pubmed]
  5. The Gv-1 locus coordinately regulates the expression of multiple endogenous murine retroviruses. Levy, D.E., Lerner, R.A., Wilson, M.C. Cell (1985) [Pubmed]
  6. Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini. Van Beveren, C., van Straaten, F., Curran, T., Müller, R., Verma, I.M. Cell (1983) [Pubmed]
  7. Short interspersed repetitive DNA elements in eucaryotes: transposable DNA elements generated by reverse transcription of RNA pol III transcripts? Jagadeeswaran, P., Forget, B.G., Weissman, S.M. Cell (1981) [Pubmed]
  8. A distant enhancer element is required for polymerase III transcription of a U6 RNA gene. Bark, C., Weller, P., Zabielski, J., Janson, L., Pettersson, U. Nature (1987) [Pubmed]
  9. Cytotoxic T lymphocyte recognition of transfected cells expressing a cloned retroviral gene. Flyer, D.C., Burakoff, S.J., Faller, D.V. Nature (1983) [Pubmed]
  10. Recombinant bacteriophages containing the integrated transforming provirus of Gardner--Arnstein feline sarcoma virus. Fedele, L.A., Even, J., Garon, C.F., Donner, L., Sherr, C.J. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  11. Endogenous retroviral env genes after N-methyl-N'-nitro-N-nitrosoguanidine treatment of mouse tumor cells: stable DNA amplification and rearrangement. Apt, D., Schreck, J., Altevogt, P. Cancer Res. (1989) [Pubmed]
  12. Defective antigen presentation by human melanoma cell lines cultured from advanced, but not biologically early, disease. Alexander, M.A., Bennicelli, J., Guerry, D. J. Immunol. (1989) [Pubmed]
  13. Cloning of a new murine endogenous retrovirus, MuERV-L, with strong similarity to the human HERV-L element and with a gag coding sequence closely related to the Fv1 restriction gene. Bénit, L., De Parseval, N., Casella, J.F., Callebaut, I., Cordonnier, A., Heidmann, T. J. Virol. (1997) [Pubmed]
  14. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Gu, H., Marth, J.D., Orban, P.C., Mossmann, H., Rajewsky, K. Science (1994) [Pubmed]
  15. Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo. Bertocci, B., De Smet, A., Weill, J.C., Reynaud, C.A. Immunity (2006) [Pubmed]
  16. DNA polymerase {eta} is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse. Delbos, F., Aoufouchi, S., Faili, A., Weill, J.C., Reynaud, C.A. J. Exp. Med. (2007) [Pubmed]
  17. Mn porphyrin-based superoxide dismutase (SOD) mimic, Mn(III)TE-2-PyP(5+), targets mouse heart mitochondria. Spasojević, I., Chen, Y., Noel, T.J., Yu, Y., Cole, M.P., Zhang, L., Zhao, Y., St Clair, D.K., Batinić-Haberle, I. Free Radic. Biol. Med. (2007) [Pubmed]
  18. Fusion proteins of Hsp70 with tumor-associated antigen acting as a potent tumor vaccine and the C-terminal peptide-binding domain of Hsp70 being essential in inducing antigen-independent anti-tumor response in vivo. Zhang, H., Huang, W. Cell Stress Chaperones (2006) [Pubmed]
  19. Immunochemical and molecular characterization of anti-RNA polymerase I autoantibodies produced by tight skin mouse. Shibata, S., Muryoi, T., Saitoh, Y., Brumeanu, T.D., Bona, C.A., Kasturi, K.N. J. Clin. Invest. (1993) [Pubmed]
  20. Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice. Gaskins, H.R., Prochazka, M., Hamaguchi, K., Serreze, D.V., Leiter, E.H. J. Clin. Invest. (1992) [Pubmed]
  21. Retroviral mRNA nuclear export elements regulate protein function and virion assembly. Swanson, C.M., Puffer, B.A., Ahmad, K.M., Doms, R.W., Malim, M.H. EMBO J. (2004) [Pubmed]
  22. Induction of high serum levels of retroviral env gene products (gp70) in mice by bacterial lipopolysaccharide. Hara, I., Izui, S., McConahey, P.J., Elder, J.H., Jensen, F.C., Dixon, F.J. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  23. Evidence for a role for DNA polymerase beta in mammalian meiosis. Plug, A.W., Clairmont, C.A., Sapi, E., Ashley, T., Sweasy, J.B. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  24. The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death. Trivedi, R.N., Almeida, K.H., Fornsaglio, J.L., Schamus, S., Sobol, R.W. Cancer Res. (2005) [Pubmed]
  25. Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100. Xia, D.J., Zhang, W.P., Zheng, S., Wang, J., Pan, J.P., Wang, Q., Zhang, L.H., Hamada, H., Cao, X. Gene Ther. (2002) [Pubmed]
  26. Necdin interacts with the Msx2 homeodomain protein via MAGE-D1 to promote myogenic differentiation of C2C12 cells. Kuwajima, T., Taniura, H., Nishimura, I., Yoshikawa, K. J. Biol. Chem. (2004) [Pubmed]
  27. The inhibition of early N-glycan processing targets TRP-2 to degradation in B16 melanoma cells. Negroiu, G., Dwek, R.A., Petrescu, S.M. J. Biol. Chem. (2003) [Pubmed]
  28. MHC antigen expression by melanomas recovered from mice treated with allogeneic mouse fibroblasts genetically modified for interleukin-2 secretion and the expression of melanoma-associated antigens. Kim, T.S., Cohen, E.P. Cancer Immunol. Immunother. (1994) [Pubmed]
  29. Mouse melanoma antigen recognized by Lyt-2- and L3T4- cytotoxic T-lymphocytes. Ono, K., Takahashi, K., Hirabayashi, Y., Itoh, T., Hiraga, Y., Taniguchi, M. Cancer Res. (1988) [Pubmed]
  30. Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Plata, F., Langlade-Demoyen, P., Abastado, J.P., Berbar, T., Kourilsky, P. Cell (1987) [Pubmed]
  31. Cell transformation and tumor induction by Abelson murine leukemia virus in the absence of helper virus. Green, P.L., Kaehler, D.A., Risser, R. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  32. Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. Blake, D.J., Love, D.R., Tinsley, J., Morris, G.E., Turley, H., Gatter, K., Dickson, G., Edwards, Y.H., Davies, K.E. Hum. Mol. Genet. (1992) [Pubmed]
  33. Mage-b4, a novel melanoma antigen (MAGE) gene specifically expressed during germ cell differentiation. Osterlund, C., Töhönen, V., Forslund, K.O., Nordqvist, K. Cancer Res. (2000) [Pubmed]
  34. Characterization of the DIM series of BALB/c preneoplasms for mouse mammary tumor virus-mediated oncogenesis. Schwartz, M.S., Medina, D. Cancer Res. (1987) [Pubmed]
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