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EXOSC10  -  exosome component 10

Homo sapiens

Synonyms: Autoantigen PM/Scl 2, Exosome component 10, P100 polymyositis-scleroderma overlap syndrome-associated autoantigen, PM-Scl, PM/Scl-100, ...
 
 
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Disease relevance of EXOSC10

  • About 50% of patients with the polymyositis/scleroderma (PM-Scl) overlap syndrome are reported to have autoantibodies to a nuclear/nucleolar particle termed PM-Scl [1].
  • IgE reactivity to rPhl p 2, 5, 6 and 11 was associated with hay fever symptoms [2].
  • Mechanism of inhibition of the retroviral protease by a Rous sarcoma virus peptide substrate representing the cleavage site between the gag p2 and p10 proteins [3].
  • The p3 peptide [amyloid beta-peptide (Abeta) 17-40/42], derived by alpha- and gamma-secretase cleavage of the amyloid precursor protein (APP), is a major constituent of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid in Down's syndrome [4].
  • In this heterologously expressed peach Pru p3, a ligand is present inside the central cavity of the protein, presumably a fatty acid that was present or produced in the culture medium of the expression organism Escherichia coli [5].
 

Psychiatry related information on EXOSC10

  • However, the importance of p3 peptide accumulation in Alzheimer's disease and its toxic properties is not clear [4].
 

High impact information on EXOSC10

  • We demonstrate that the homolog of the Rrp4p exosome subunit is also a component of the PM-Scl complex, thereby providing compelling evidence that the yeast exosome and human PM-Scl complexes are functionally equivalent [6].
  • The absence of the nuclear-specific exosome component, Rrp6p, from the rna14.1 strain gave a very different phenotype [7].
  • Molecular characterization of an autoantigen of PM-Scl in the polymyositis/scleroderma overlap syndrome: a unique and complete human cDNA encoding an apparent 75-kD acidic protein of the nucleolar complex [1].
  • Among sera from 39 patients with anti-PM-Scl, 23 recognized the 100-kD band in immunoblot against HeLa cell extract, 16 of which also stained the 70-kD band [8].
  • We present evidence that the maize p1 and p2 genes were generated by duplication of an ancestral p gene (p(pre)) and its downstream sequences; the duplicated 3' flanking sequences were inserted upstream of the p(pre) gene, thereby changing its transcription pattern [9].
 

Chemical compound and disease context of EXOSC10

  • Transcription of the Azotobacter vinelandii algD gene, which encodes GDP-mannose dehydrogenase (the rate-limiting enzyme of alginate synthesis), starts from three sites: p1, p2, and p3 [10].
  • To prepare tripod-like assemblies, phage were engineered to express trimeric leucine zippers as p3 fusion proteins [11].
  • The coding regions of Der p 4 and Eur m 4 were cloned into the pET expression vector and recombinant histidine-tagged proteins expressed in Escherichia coli [12].
  • CD4+ T cells from patients with systemic sclerosis are stimulated by human type I collagen, and immunoglobulins from some patients with systemic sclerosis bind retroviral proteins, the terminal galactosyl (alpha 1-3)-galactose disaccharide of laminin, or a 138 amino acid region of the PM-Scl antigen [13].
 

Biological context of EXOSC10

  • In fact, a STS (G25404) located 54.6 cR from the top of human chromosome 1 was found to contain PMSCL2 sequence upon BLAST search [14].
  • To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI [15].
  • To elucidate the molecular evolution of the p1 gene in relation to its expression and possible functions in maize and teosinte, we have isolated a second maize gene (p2) that is highly homologous with the p1 gene, and a related gene (p2-t) from Zea mays subsp parviglumis [9].
  • In contrast, Rrp47p is not required for the Rrp6p-dependent degradation of 3'-extended nuclear pre-mRNAs or the cytoplasmic 3'-->5' mRNA decay pathway [16].
  • Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations [17].
 

Anatomical context of EXOSC10

  • Approximately 30% of analogues at either Leu57 (p1), Ala60 (p4), or Asn62 (p6) residues exhibited TCR agonism to stimulate various magnitudes of proliferative responses in the T cell clone, and analogues exhibiting TCR antagonism are rare in these three residues [18].
  • RESULTS: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal - endocrine) and pure ductal type (p1 = 0.001, p2 < 0.0005, p3 = 0.046 and p4 < 0.0005 respectively) [19].
  • Fibroblasts expressing APP695 using the same SFV vector mainly produced a related 3 kDa p3 peptide, a nonamyloidogenic fragment [20].
  • Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells [21].
  • At the epitope level, panel studies showed that peptides p2, p3, and p11 were presented to T cells by HLA-DR-matched as well as mismatched allogeneic antigen-presenting cells, thus representing promiscuous epitopes [22].
 

Associations of EXOSC10 with chemical compounds

  • Testing for the IgE reactivity to the glycan of the native Phl p 4 allergen showed a possible interference with prevalence and value estimation [23].
  • In addition, phenylalanine substitutions at tyrosine 607 and 580 reduced the p1 and p2 phosphopeptides in vivo, respectively [24].
  • These responses were similar to those observed with trypsin and a specific PAR-2 agonist and were related to the serine protease activity of Der p3 and Der p9 [21].
  • N-terminal sequence analysis (18 residues) indicated homology with the mite tryptic allergen, Der p 3, and the chymotryptic allergen, Der p 6 [25].
  • Phospholipid-binding assays of p2-derived synthetic peptides suggested that phosphatidylserine binding was not affected by the mutations studied [26].
 

Co-localisations of EXOSC10

 

Other interactions of EXOSC10

  • The PM-Scl-100-containing PNBs were translocated at later times to nucleoli as opposed to the fibrillarin-containing PNBs [27].
  • The frequencies of some rare autoantibodies (PCNA, PL-4, SL, PM-Scl, Scl-70, Jo-1) in systemic connective tissue diseases of mixed Yugoslav population are demonstrated [28].
  • Immunoprecipitation of epitope-tagged Rrp47p confirmed its interaction with the exosome and revealed its association with Rrp6p, a 3'-->5' exonuclease specific to the nuclear exosome fraction [16].
  • Autoantibodies against most relevant muscle specific (Jo-1, Mi-2) and non-specific antigens (PM-Scl, U1RNP, native Ro, Ro60, Ro52, and La) were detected with one or more detection techniques: counter-immunoelectrophoresis, enzyme-linked immunoassay, immunoblot and immunoprecipitation, each using different antigen preparations (native, recombinant) [29].
 

Analytical, diagnostic and therapeutic context of EXOSC10

  • The two complexes are similar in size, and biochemical fractionation and indirect immunofluorescence experiments show that, in both yeast and humans, nuclear and cytoplasmic forms of the complex exist that differ only by the presence of the Rrp6p/PM-Scl100 subunit exclusively in the nuclear complex [6].
  • In addition, rabbit antibodies raised to recombinant fusion protein reacted in immunofluorescence, immunoblotting, and immunoprecipitation with the characteristic features displayed by human anti-PM-Scl sera [1].
  • METHODS: Serum samples obtained from patients with the PM/scleroderma overlap syndrome and from patients with several other diseases were analyzed for the presence of autoantibodies reactive with recombinant PM-Scl-100 and PM-Scl-75 (both the original and the longer form) proteins, in an enzyme-linked immunosorbent assay (ELISA) [30].
  • Evaluation of recombinant and native timothy pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- specific IgG4 antibodies induced by subcutaneous immunotherapy with timothy pollen extract in allergic patients [31].
  • Der p 1 and Der p 2 cDNAs were PCR amplified and sequenced [32].

References

  1. Molecular characterization of an autoantigen of PM-Scl in the polymyositis/scleroderma overlap syndrome: a unique and complete human cDNA encoding an apparent 75-kD acidic protein of the nucleolar complex. Alderuccio, F., Chan, E.K., Tan, E.M. J. Exp. Med. (1991) [Pubmed]
  2. IgE reactivity pattern to timothy and birch pollen allergens in Finnish and Russian Karelia. Movérare, R., Petays, T., Vartiainen, E., Haahtela, T. Int. Arch. Allergy Immunol. (2005) [Pubmed]
  3. Mechanism of inhibition of the retroviral protease by a Rous sarcoma virus peptide substrate representing the cleavage site between the gag p2 and p10 proteins. Cameron, C.E., Grinde, B., Jentoft, J., Leis, J., Weber, I.T., Copeland, T.D., Wlodawer, A. J. Biol. Chem. (1992) [Pubmed]
  4. Abeta 17-42 in Alzheimer's disease activates JNK and caspase-8 leading to neuronal apoptosis. Wei, W., Norton, D.D., Wang, X., Kusiak, J.W. Brain (2002) [Pubmed]
  5. Crystal structure of peach Pru p 3, the prototypic member of the family of plant non-specific lipid transfer protein pan-allergens. Pasquato, N., Berni, R., Folli, C., Folloni, S., Cianci, M., Pantano, S., Helliwell, J.R., Zanotti, G. J. Mol. Biol. (2006) [Pubmed]
  6. The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Allmang, C., Petfalski, E., Podtelejnikov, A., Mann, M., Tollervey, D., Mitchell, P. Genes Dev. (1999) [Pubmed]
  7. Processing of 3'-extended read-through transcripts by the exosome can generate functional mRNAs. Torchet, C., Bousquet-Antonelli, C., Milligan, L., Thompson, E., Kufel, J., Tollervey, D. Mol. Cell (2002) [Pubmed]
  8. Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen. Ge, Q., Frank, M.B., O'Brien, C., Targoff, I.N. J. Clin. Invest. (1992) [Pubmed]
  9. A segmental gene duplication generated differentially expressed myb-homologous genes in maize. Zhang, P., Chopra, S., Peterson, T. Plant Cell (2000) [Pubmed]
  10. The global regulators GacA and sigma(S) form part of a cascade that controls alginate production in Azotobacter vinelandii. Castañeda, M., Sánchez, J., Moreno, S., Núñez, C., Espín, G. J. Bacteriol. (2001) [Pubmed]
  11. Assembly of multimeric phage nanostructures through leucine zipper interactions. Sweeney, R.Y., Park, E.Y., Iverson, B.L., Georgiou, G. Biotechnol. Bioeng. (2006) [Pubmed]
  12. Molecular characterization of the group 4 house dust mite allergen from Dermatophagoides pteronyssinus and its amylase homologue from Euroglyphus maynei. Mills, K.L., Hart, B.J., Lynch, N.R., Thomas, W.R., Smith, W. Int. Arch. Allergy Immunol. (1999) [Pubmed]
  13. Immunologic aspects of scleroderma. Needleman, B.W. Current opinion in rheumatology. (1992) [Pubmed]
  14. Structure and localization of mouse Pmscl1 and Pmscl2 genes. Bliskovski, V., Liddell, R., Ramsay, E.S., Miller, M.J., Mock, B.A. Genomics (2000) [Pubmed]
  15. Nuclear mRNA degradation pathway(s) are implicated in Xist regulation and X chromosome inactivation. Ciaudo, C., Bourdet, A., Cohen-Tannoudji, M., Dietz, H.C., Rougeulle, C., Avner, P. PLoS Genet. (2006) [Pubmed]
  16. Rrp47p is an exosome-associated protein required for the 3' processing of stable RNAs. Mitchell, P., Petfalski, E., Houalla, R., Podtelejnikov, A., Mann, M., Tollervey, D. Mol. Cell. Biol. (2003) [Pubmed]
  17. Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations. Oddis, C.V., Okano, Y., Rudert, W.A., Trucco, M., Duquesnoy, R.J., Medsger, T.A. Arthritis Rheum. (1992) [Pubmed]
  18. Response of a human T cell clone to a large panel of altered peptide ligands carrying single residue substitutions in an antigenic peptide: characterization and frequencies of TCR agonism and TCR antagonism with or without partial activation. Chen, Y.Z., Matsushita, S., Nishimura, Y. J. Immunol. (1996) [Pubmed]
  19. Pancreatic-polypeptide in the human pancreas: expression and quantitative variation during development and in ductal adenocarcinoma. Tamiolakis, D., Simopoulos, C., Kotini, A., Venizelos, I., Jivannakis, T., Papadopoulos, N. Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové. (2003) [Pubmed]
  20. Amyloidogenic processing of the human amyloid precursor protein in primary cultures of rat hippocampal neurons. Simons, M., de Strooper, B., Multhaup, G., Tienari, P.J., Dotti, C.G., Beyreuther, K. J. Neurosci. (1996) [Pubmed]
  21. Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells. Sun, G., Stacey, M.A., Schmidt, M., Mori, L., Mattoli, S. J. Immunol. (2001) [Pubmed]
  22. Identification and HLA restriction of naturally derived Th1-cell epitopes from the secreted Mycobacterium tuberculosis antigen 85B recognized by antigen-specific human CD4(+) T-cell lines. Mustafa, A.S., Shaban, F.A., Abal, A.T., Al-Attiyah, R., Wiker, H.G., Lundin, K.E., Oftung, F., Huygen, K. Infect. Immun. (2000) [Pubmed]
  23. Skin test with a timothy grass (Phleum pratense) pollen extract vs. IgE to a timothy extract vs. IgE to rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5, rPhl p 6, rPhl p 7, rPhl p 11, and rPhl p 12: epidemiological and diagnostic data. Mari, A. Clin. Exp. Allergy (2003) [Pubmed]
  24. The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor. Hayashi, H., Nishioka, Y., Kamohara, S., Kanai, F., Ishii, K., Fukui, Y., Shibasaki, F., Takenawa, T., Kido, H., Katsunuma, N. J. Biol. Chem. (1993) [Pubmed]
  25. The isolation and characterization of a novel collagenolytic serine protease allergen (Der p 9) from the dust mite Dermatophagoides pteronyssinus. King, C., Simpson, R.J., Moritz, R.L., Reed, G.E., Thompson, P.J., Stewart, G.A. J. Allergy Clin. Immunol. (1996) [Pubmed]
  26. Conformation- and fusion-defective mutations in the hypothetical phospholipid-binding and fusion peptides of viral hemorrhagic septicemia salmonid rhabdovirus protein G. Rocha, A., Ruiz, S., Tafalla, C., Coll, J.M. J. Virol. (2004) [Pubmed]
  27. Effects of anti-PM-Scl 100 (Rrp6p exonuclease) antibodies on prenucleolar body dynamics at the end of mitosis. Fomproix, N., Hernandez-Verdun, D. Exp. Cell Res. (1999) [Pubmed]
  28. The significance of some immunoserologic diagnostic tests in systemic diseases. Rozman, B., Kveder, T., Lestan, B. Acta Med. Austriaca (1988) [Pubmed]
  29. Immunoserological aspects of idiopathic inflammatory muscle disease. Rozman, B., Bozic, B., Kos-Golja, M., Plesivcnik-Novljan, M., Kveder, T. Wien. Klin. Wochenschr. (2000) [Pubmed]
  30. PM-Scl-75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome. Raijmakers, R., Renz, M., Wiemann, C., Egberts, W.V., Seelig, H.P., van Venrooij, W.J., Pruijn, G.J. Arthritis Rheum. (2004) [Pubmed]
  31. Evaluation of recombinant and native timothy pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- specific IgG4 antibodies induced by subcutaneous immunotherapy with timothy pollen extract in allergic patients. Rossi, R.E., Monasterolo, G. Int. Arch. Allergy Immunol. (2004) [Pubmed]
  32. Allergens of wild house dust mites: environmental Der p 1 and Der p 2 sequence polymorphisms. Smith, W.A., Hales, B.J., Jarnicki, A.G., Thomas, W.R. J. Allergy Clin. Immunol. (2001) [Pubmed]
 
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